0.313) or OS (p = 0.081); however, lines of salvage and response

prior to ASCT remain signiﬁcantly prognostic for PFS (>1 line of

salvage: HR 2.14, 95% CI 1.59‐2.87, p < 0.001; non‐CR: HR 1.61, 95%

CI 1.26‐2.05, p < 0.001) and OS (>1 line of salvage: HR 2.25, 95% CI

1.66‐3.05, p < 0.001; non‐CR: HR 1.63, 95% CI 1.26‐2.12, p < 0.001).

Conclusions: In patients with RR DLBCL following frontline immu-

nochemotherapy, requiring more than 1 line of salvage therapy and

failure to achieve CR are strong independent risk factors for poor

PFS and OS after ASCT. Novel therapies such as CAR‐T cell therapy

should be studied in this population.

EA – previously submitted to ASCO 2021.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Combination

Therapies, Stem Cell Transplant

Conﬂicts of interests pertinent to the abstract

M. Kharfan‐Dabaja

Consultant or advisory role: Daiichi Sankyo

187 | AUTOLOGOUS TRANSPLANT IN ELDERLY PATIENTS

WITH R/R AGGRESSIVE LYMPHOMA SELECTED BY SIMPLIFIED

CGA: THE RECANZ PROSPECTIVE PHASE 2 STUDY BY THE

FONDAZIONE ITALIANA LINFOMI

A. Tucci

, G. Musuraca

, F. Cavallo

, V. R. Zilioli

, M. Zanni

S. Pelliccia

, D. Mannina

, M. Michieli

, D. Vallisa

, M. Tani

F. Merli

, F. Re

, L. Marcheselli

, G. Campostrini

, C. Pagani

D. Grimaldi

, E. V. Liardo

, A. Re

, M. C. Cox

, G. Rossi

ASST Spedali Civili Brescia, Hematology Division, Brescia, Italy,

IRCCS

Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”,

Hematology Unit, Meldola (FC), Italy,

University of To‐rino/AOU “Città

della Salute e della Scienza di Torino”, Division of Hematology,

Department of Molecular Biotechnologies and Health Sciences, Torino,

Italy,

ASST Grande Ospedale Metropolitano Niguarda, Division of

Hematology, Milano, Italy,

A.O. SS. Antonio e Biagio e Cesare Arrigo,

Division of Hematology, Alessandria, Italy,

Hospital Sant’Andrea –

Sapienza, Rome, Hematology, University, Roma, Italy,

Azienda

Ospedaliera Papardo, Unit of Hematology, Messina, Italy,

Aviano (PN),

Haematology Transplant and Cell Therapy Unit, Aviano (PN), Italy,

Ospedale Guglielmo da Saliceto, Division of Hematology, Piacenza, Italy,

Ospedale delle Croci, Department of Hematology, Ravenna, Italy,

Azienda Unità Sanitaria Locale – IRCCS, Hematology Unit, Reggio

Emilia, Italy,

AOU di Parma, Hematology Unit, Parma, Italy,

Fondazione Italiana Linfomi Onlus, Fondazione Italiana Linfomi Onlus,

Modena, Italy,

University Hospital Sant’Andrea – Sapienza, Hematology,

Roma, Italy

Introduction: Relapsed/refractory (R/R) aggressive B cell lym-

phoma has a poor prognosis especially in the post‐Rituximab era.

Platinum‐based salvage treatment followed by autologous stem

cell transplantation (ASCT) is still standard treatment in young

patients (pts). However, more than 60% of pts are older than 65

and represent an unmet need. We have recently demonstrated

that a simpliﬁed comprehensive geriatric assessment (sCGA) can

identify elderly lymphoma pts ﬁt for intensive ﬁrst‐line treatment.

We have conducted a multicentre study aiming at evaluating

the feasibility of an ASCT program in elderly R/R aggressive

lymphoma pts.

Methods: Patients with R/R aggressive lymphoma after one line of

treatment, age 65‐75, and FIT to sCGA were included. Recommended

treatments were R‐DHAP, R‐ICE or gemcitabine‐containing

264

SUPPLEMENT ABSTRACTS

regimens, with PBSC mobilisation after 1‐2 cycles. Patients FIT to a

second sCGA evaluation achieving at least partial response after 3

salvage courses were eligible for ASCT and were conditioned with

either BEAM or FEAM.

Results: Seventy pts were enrolled by 16 FIL centres from May

2014 to August 2019. Forty‐three pts did not reach ASCT because

of progressive (32) or stable (4) disease, death (heart failure and

septic shock) (2), personal/physician decision (4/1). ASCT was

performed in 27 pts; a median of 5.6 x 106 CD34/Kg were

infused. Table 1a shows their demographic and clinical character-

istics. No differences emerged between pts reaching ASCT or not.

By intention to treat analysis 2‐y overall survival (OS) and PFS of

the 70 pts enrolled were 65% (95%CI: 50‐76%) and 34% (95%CI:

22‐46%) respectively, without differences according to age (table

1b). After a median of 27 months, OS after ASCT was 79% (95CI:

51‐86%) and EFS 56% (95CI: 32‐75%). Twenty‐four pts obtained a

CR; three pts progressed 1‐8 months after ASCT and died. Most

common non‐hematologic grade 3‐4 AE were gastrointestinal

(11%) and infectious (6.5%).

Conclusion: This study conﬁrms the poor response to II‐line

chemotherapy of elderly pts with R/R aggressive lymphoma

selected by sCGA. However, it highlights the feasibility and high

efﬁcacy of ASCT in responding pts. These results represent a useful

comparator for the evaluation of feasibility and efﬁcacy of innovative

approaches like CAR‐T cells or bispeciﬁc antibodies in the same age

groups.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma Stem Cell

Transplant

No conﬂicts of interest pertinent to the abstract.

188 | ALLOGENEIC HEMATOPOIETIC STEM CELLS

TRANSPLANTATION FOR NON‐HODGKIN'S LYMPHOMA IN

SWITZERLAND. 35 YEARS OF EXPERIENCE 1985‐2020. FOR SBST

WORKING GROUP

M. Nabergoj

, B. Grandjean

, P. Stakia

, A. Stern

, M. Medinger

H. Baldomero

, S. Masouridi‐Levrat

, C. Dantin

, A. Rovo

K. Ritter

, U. Schanz

, J. Passweg

, Y. Chalandon

, E. Rebmann

Chigrinova

University Hospital of Geneva, HUG, Hematology, Geneva, Switzerland,

University Hospital of Bern, Inselspital, Hematology and central

laboratory, Bern, Switzerland,

Réseau hospitalier neuchâtelois, Oncology

‐hematology department, Neuchâtel, Switzerland,

University Hospital of

Basel, Hematology, Basel, Switzerland,

University Hospital of Zurich,

Hematology, Zurich, Switzerland

Background: despite the development of new highly effective

treatments in the ﬁeld of Non‐Hodgkin's lymphoma (NHL), allo-

geneic hematopoietic stem cell transplantation (alloHSCT) still

remains a potentially curative option for virtually all type of NHL.

Due to concerns about its high toxicity, alloHSCT in NHL is

reserved as the ultimate line of treatment. Introduction of reduced

intensity conditioning regimens, usage of T‐depletion methods,

amelioration of supportive care and graft‐versus –host (GvHD)

disease treatment have globally decreased the NRM rates, making

the use of alloHSCT an attractive alternative in a setting of

relapse/refractory NHL. Here we report the 35 years of Swiss

experience in alloHSCT for NHL.

Materials and Methods: The study included 301 patients who

received alloHSCT for NHL in one of the three University Hospitals

of Switzerland (Zurich, Basel and Geneva) between September 1985

and May 2020. The primary endpoint was OS. Secondary endpoints

were relapse free survival (RFS), non‐relapse mortality (NRM),

relapse incidence (RI), acute (aGVHD) and chronic (cGVHD) rates,

that were assessed in univariate analysis.

Results: Median follow‐up was 61 months (24‐112). The median

age of patients at the time of alloHSCT was 51 years (17‐72), with

male gender prevalence 206 (68%). B‐cell NHL were diagnosed in

217 (72%) cases, with the most frequent being DLBCL and CLL

subtypes (76 and 53 cases respectively). T‐cell NHL were indica-

tion for alloHSCT in 84 (28%) cases. Prior autologous HSCT was

performed in 130 (43%) of patients. A good performance sta-

tus, according to Karnofsky index (≥80) was reported in 259

(90%). Hundred forty‐four (48%) patients were in CR and 32

(22%) of those were in ﬁrst CR. A reduced conditioning regimen

(RIC) was applied in 167 (56%) patients. TBI was part of condi-

tioning regimen in 132 (44%) patients. Stem cell source was pe-

ripheral blood in 261 (87%) transplants. Donor was an HLA‐

identical sibling or an HLA‐matched unrelated donor for 159

(53%) and 74 (25%) transplants, respectively. Successful neutrophil

engraftment occurred in 273 (98%) patients in a median of 14

days (12‐18).

Survival analysis: 5‐ and 10‐years OS was 55% (SE ± 5.6) and 51%

(SE ± 6.7), respectively, and 5‐ and 10‐years RFS was 44% (±7.1) and

38% (SE±8.9). According to the univariate analysis, patients trans-

planted at younger age (<50 years) in a good performance status

(Karnofsky index ≥80), those in CR, especially in the ﬁrst one (vs.

second or above) and those transplanted with a HLA‐matched sibling

showed signiﬁcantly better OS and RFS survivals (p < 0.05). 5‐ and

10‐years NRM was 24% (±2.7) and 28% (±3.0), respectively, and RI ‐

31% (±2.9) and 35% (±3.2).

Conclusions: Our retrospective analysis of a large group of mixed‐

type NHL with an extended follow up (maximum of 25 years) con-

ﬁrms the efﬁcacy of alloHSCT with promising long‐term OS, RFS and

acceptable NRM rate.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Aggressive T‐

cell non‐Hodgkin lymphoma, Stem Cell Transplant

No conﬂicts of interest pertinent to the abstract.

SUPPLEMENT ABSTRACTS

265

HODGKIN LYMPHOMA

189 | AMAHRELIS : ADCETRIS MAINTENANCE AFTER

AUTOLOGOUS STEM CELL TRANSPLANTATION IN HODGKIN

LYMPHOMA : A REAL LIFE STUDY FROM SFGMTC AND LYSA

GROUPS

A. Marouf

, A. S. Cottereau

, S. Kanoun

, P. Deschamps

, P. Franchi

M. Meignan

, D. Sibon

, T. Gastinne

, C. Borel

, M. Hammoud

G. Sicard

, R. Gille

, D. Cavalieri

, A. Stamatoullas

, L. Clement

J. Lazarovici

, A. Chauchet

, L. M. Fornecker

, S. Amorin

M. Rocquet

, N. Raus

, B. Burroni

, M. T. Rubio

, O. Casasnovas

G. Cartron

, D. Bouscary

, P. Brice

, H. Ghesquieres

J. Tamburini

, B. Deau

Cochin Hospital, Paris University, Hematology Unit, Paris, France,

Cochin Hospital, Assistance Publique‐Hôpitaux de Paris (AP‐HP), Paris

Descartes University, Department of Nuclear Medicine, Paris, France,

Institut universitaire du cancer Toulouse‐Oncopole, Nuclear Medecine

Unit, Toulouse, France,

Hôpital Henri Mondor, Paris Est University,

Lymphoma Study Association Imaging, Créteil, France,

Necker Hospital,

Paris University, Department of Hematology, Paris, France,

Nantes Uni-

versity Hospital, Department of Hematology, Nantes, France,

Institut

universitaire du cancer Toulouse‐ Oncopole, Hematology, Toulouse,

France,

Lymphoid Malignancies Unit, Hôpital Henri Mondor, Hematology,

Creteil, France,

Aix‐Marseille University, Hematology, Marseille, France,

Centre Léon Berard, Hematology, Lyon, France,

Centre Hospitalier

Universitaire Estaing, Hematology, Clermont Ferrand, France,

Centre

Henri Becquerel, Hematology, Rouen, France,

CHRU Nancy Brabois,

Hematology, Vandoeuvre Les Nancy, France,

Institut Gustave Roussy,

Hematology, Villejuif, France,

CHU Besançon, Hematology, Besançon,

France,

Strasbourg University Hospital,INSERM S‐1113, Hematology,

Strasbourg, France,

Hopital Saint Vincent de Paul, Hematology, Lille,

France,

Hopital Lyon Sud, Hematology, Pierre Benite, France,

Cochin

Hospital, APHP, Centre de recherche des Cordeliers, Sorbonne University,

INSERM, Paris University, Pathology, Paris, France,

CHRU Nancy, CNRS

UMR 7365, Équipe 6, Biopôle de L'Université de Lorraine, Hematology,

Vandoeuvre Les Nancy, France,

Dijon University Hospital, INSERM UMR

1231, Hematology, Dijon, France,

University of Montpellier, Hematol-

ogy, Montpellier, France,

Saint Louis Hospital, Paris university, Hema-

tology, Paris, France,

Université de Paris, Institut Cochin, INSERM

FIGURE 1 10‐years overall survival and non‐relapse mortality

266

SUPPLEMENT ABSTRACTS

U1016, F‐75014 Paris, Translational Research Centre in Onco‐

hematology, Faculty of Medicine, University of Geneva, 1211, Hematol-

ogy, Geneva, Switzerland

Introduction: AETHERA study (Moskowitz, Lancet 2015) showed

that Brentuximab Vedotin (BV) maintenance after autologous stem

cell transplantation (ASCT) improved progression free survival (PFS)

in BV‐naive refractory/relapsed (R/R) Hodgkin lymphoma (HL) pa-

tients. However, since BV approval for R/R HL, many patients are

receiving salvage BV before ASCT, alone or combined with chemo-

therapy. In AMAHRELIS study, we investigated the outcome of pa-

tients mostly treated with BV in salvage and maintenance post‐

ASCT.

Methods: We conducted this observational retrospective cohort

study in 25 centers. Inclusion criteria were R/R HL patients who

received at least two infusions of BV after ASCT, at the exclusion of

patients in progression after transplant. Among 1134 patients who

underwent ASCT for R/R HL between 2012 and 2017 based on the

French society of bone marrow transplantation database, data were

available for 794 (70%) patients. FDG‐PET scan at relapse and before

transplantation were centrally reviewed and metabolic complete

remission (mCR) was deﬁned by a Deauville score <4. As primary

objective, the 2 years‐PFS was assessed.

Results: A total of 115 patients were enrolled. 95% met inclusion

criteria for BV maintenance according to the AETHERA study as

primary refractory disease (43%), early relapse (27%) or extranodal

disease (49%). The mean number of BV injections after ASCT was 11

(3‐18). Patients characteristics were : median age of 34 y (16‐68y),

54% were male, 43% patients had PRD, 28% an ER and 29% a relapse

>12 months. Notably, 70% of patients received BV as salvage ther-

apy. Among 91 patients eligible for FDG‐PET centrally review, 89%

(81/91) achieved a mCR before ASCT. The median follow‐up period

was 35 months. The 2‐years survival for the whole cohort was 75,3%

for PFS (95% CI : 68,4‐84,3) and 96,4% for OS (95% CI : 94,2‐100)

SUPPLEMENT ABSTRACTS

267

(Figures A‐B). The use of BV as part of salvage therapy before

transplant had no impact on outcome.

High risk patients according to the Lysa prognosis score, as

either primary refractory disease or early relapse and disseminated

disease, correlated signiﬁcantly with a lower PFS. A subgroup anal-

ysis was subsequently conducted from two real life studies ‐ Amah-

relis and HR2009 (Deau, BJH 2018) – to compare two consolidation

strategies in high risk patients, either BV maintenance or a second

ASCT. This analysis was performed after one‐to‐one propensity score

matching generated 24 pairs with well‐balanced baseline confound-

ing factors and with an adjustment on the propensity score on the

whole population, and showed a similar outcome on PFS, whereas BV

maintenance offers a better OS than a second ASCT (Figures C‐D).

Conclusion: From the real‐life AMAHRELIS study, we conﬁrmed the

favorable outcome of R/R HL patients in the era of BV maintenance.

Future studies incorporating BV strategies with immune checkpoint

inhibitors might improve outcome in high risk patients.

Keywords: Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

B. Deau

Consultant or advisory role: Roche, Takeda

Research funding: Takeda

190 | LONG‐TERM FOLLOW‐UP AND BIOMARKER ANALYSES

OF BRENTUXIMAB VEDOTIN AND DHAP IN RELAPSED/

REFRACTORY HODGKIN LYMPHOMA PATIENTS: THE HOVON/

LLPC TRANSPLANT BRAVE STUDY

J. Driessen

, M. J. Kersten

, L. Visser

, A. van den Berg

J. M. Zijlstra

, S. H. Tonino

, G. J. Zwezerijnen

, R. Boellaard

P. J. Lugtenburg

, M. Hutchings

, M. Nijland

, R. D. Liu

F. Morschhauser

, P. Brice

, T. Gastinne

, D. de Jong

A. Hagenbeek

, W. J. Plattel

, A. Diepstra

Amsterdam UMC, University of Amsterdam, LYMMCARE, Cancer Center

Amsterdam, Department of Hematology, Amsterdam, Netherlands,

University of Groningen, University Medical Center Groningen,

Department of Pathology and Medical Biology, Groningen, Netherlands,

Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center

Amsterdam, Department of Hematology, Amsterdam, Netherlands,

Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center

Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam,

Netherlands,

Erasmus MC Cancer Institute, University Medical Center,

Department of Hematology, Rotterdam, Netherlands,

Rigshospitalet,

Department of Hematology, Copenhagen, Denmark,

University of

Groningen, University Medical Center Groningen, Department of

Hematology, Groningen, Netherlands,

Centre Hospitalier Universitaire,

Department of Hematology, Lille, France,

Hopital Saint Louis,

Department of Hematology, Paris, France,

Centre Hospitalier

Universitaire, Department of Hematology, Nantes, France,

Amsterdam

UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam,

Department of Pathology, Amsterdam, Netherlands

Background: Patients with relapsed/refractory classical Hodgkin

lymphoma (r/r cHL) generally have a poor prognosis. We have shown

that brentuximab vedotin (BV) in combination with DHAP (dexa-

methasone, cytarabine, cisplatin) is highly effective with manageable

toxicity. Here we present the long‐term follow‐up, and also thymus

and activation regulated chemokine (TARC) and metabolic tumor

volume (MTV) analyses.

Methods: Patients were treated with 3 cycles of BV‐DHAP followed by

autologous stem‐cell transplant (ASCT). Serum was collected at base-

line, after each cycle, after ASCT and during follow‐up. Soluble (s)TARC

was measured byELISA. Immunohistochemical (IHC) staining was done

for TARC on the lymph node biopsy at baseline. Baseline

F‐FDG‐

PET‐CT scans were analyzed for MTV using a threshold of standard

uptake value (SUV) ≥4.0. Prognostic value of biomarkers for time to

progression (TTP) was assessed by log‐rank survival analysis.

Results: Sixty‐ﬁve patients, of whom 46% had primary refractory

disease, were included. Central pathology review conﬁrmed cHL

diagnosis in 58/65 patients. Patients with other histologies were

excluded from biomarker analyses, but not from clinical evaluation

per intention to treat. After a median follow‐up of 39 months, the 3‐

year progression free survival (PFS) was 77% (95%CI: 70‐88) and the

overall survival (OS) was 95% (95%CI: 90‐100).

Of conﬁrmed cHL patients (n = 58), seven patients (12%) had

weak or no TARC IHC staining in the Hodgkin‐Reed Sternberg (HRS)

cells and showed lower serum sTARC levels compared to patients

with positive TARC staining (median 608 vs 3701 pg/mL; p = 0.04).

cHL patients with no/weak TARC staining had a lower 3‐year TTP

rate (57% vs 93%, respectively; p < 0.001).

Based on levels in healthy controls, cHL patients with a baseline sTARC

< 1000 pg/ml (n = 14) were excluded in the subsequent sTARC ana-

lyses. sTARC decreased signiﬁcantly after 1 cycle of BV‐DHAP (p <

0.001; Figure 1A), and patients with sTARC < 1000 pg/mL after 1 cycle

of BV‐DHAP had a 3‐year TTP of 91% vs 55% for patients with sTARC

≥1000 pg/mL at that timepoint (p = 0.01; Figure 1B).

Baseline MTV correlated with baseline sTARC (r = 0.53; p < 0.001).

Interim PET evaluation after 3 cycles of BV‐DHAP showed a a

complete metabolic response (CMR) in 47 patients and a partial

response (PR) in 5 patients. Patients with a CMR had a 3‐year TTP of

93% vs 40% for patients with a PR (p < 0.001).

Conclusion: Long‐term follow‐up of r/r cHL patients treated with BV‐

DHAP shows a high 3‐year PFS and OS. Serum sTARC correlates with

baseline MTV and can be used as an early response marker already

after 1 cycle of BV‐DHAP. Interim PET status is a strong prognostic

factor for post‐ASCT TTP. In addition, we have identiﬁed low TARC

expression in HRS cells as a possible poor prognostic factor. Risk

assessment using different biomarkers could help guide treatment

decisions in an era with new targeted treatment options for r/r cHL.

EA – previously submitted to EHA 2021.

The research was funded by: The study drug (BV) was provided for

the study and the study was funded by Takeda. Takeda did not have

268

SUPPLEMENT ABSTRACTS

any inﬂuence on the analysis of the data or the interpretation of the

results.

Keywords: Diagnostic and Prognostic Biomarkers, PET‐CT, Hodgkin

lymphoma

Conﬂicts of interests pertinent to the abstract

J. Driessen

Educational grants: Takeda (ASH conference 2019)

M. J. Kersten

Honoraria: Millennium/Takeda

Research funding: Millennium/Takeda

J. M. Zijlstra

Consultant or advisory role: Millennium/Takeda

Educational grants: Takeda (ASH 2019)

P. J. Lugtenburg

Consultant or advisory role: Millennium/Takeda

Research funding: Millennium/Takeda

M. Hutchings

Consultant or advisory role: Millennium/Takeda

Research funding: Millennium/Takeda

P. Brice

Honoraria: Millennium/Takeda

Research funding: Millennium/Takeda

T. Gastinne

Honoraria: Millennium/Takeda

D. de Jong

Consultant or advisory role: Millennium/Takeda

SUPPLEMENT ABSTRACTS

269

A. Hagenbeek

Consultant or advisory role: Millennium/Takeda

Honoraria: Millennium/Takeda

Research funding: Millennium/Takeda

A. Diepstra

Consultant or advisory role: Millennium/Takeda

Research funding: Millennium/Takeda

191 | BEGEV SALVAGE REGIMEN IN RELAPSED/

REFRACTORY CLASSICAL HODGKIN LYMPHOMA: A REAL‐LIFE

EXPERIENCE

A. Morigi

, V. Stefoni

, L. Argnani

, M. Carella

, B. Casadei

, G. Lolli

A. Broccoli

, C. Pellegrini

, L. Nanni

, P. E. Coppola

, M. Gentilini

G. Bagnato

, P. L. Zinzani

IRCCS Azienda Ospedaliero‐Universitaria di Bologna Istituto di

Ematologia “Seràgnoli”, and Dipartimento di Medicina Specialistica,

Diagnostica e Sperimentale Università di Bologna, n/a, Bologna, Italy

Introduction: Any strategy aimed at achieving a minimal disease

status, and at speciﬁcally obtaining a positron emission tomography‐

negative status before autologous stem cell transplantation (ASCT)

without severe toxicity in primary relapsed/refractory Hodgkin

lymphoma (HL) patients would represent a major advance in the

overall management in this setting.

Methods: A single‐center observational retrospective study was

conducted to assess effectiveness and safety of BEGEV (bendamus-

tine, gemcitabine and vinorelbine) regimen as ﬁrst salvage setting

prior to ASCT in HL patients.

Results: In total, 23 patients (14 men and 9 women) were treated in

our institution between October 2017 and September 2019. Me-

dian age at BEGEV time was 39.6 years (range 17.2– 70.0), and the

median time from frontline therapy to ﬁrst cycle of BEGEV was 1.3

months (range 1–8). At the end of BEGEV treatment, 21 out of the

23 patients, achieved a complete response (CR), with an ORR of

91.3%. All the patients underwent ASCT. With a median follow‐up

time of 15 months, 2 CR patients had disease relapse, yielding an

estimated DFS of 86.7% at 26.6 months. The estimated OS was

95.5% at 27 months and the 2‐year PFS was 81.4%, respectively.

Response to ﬁrst‐line chemotherapy did not signiﬁcantly inﬂuence

prognosis. BEGEV regimen was well tolerated by most patients, and

reversible hematological toxic effects were the most common

adverse events.

Conclusions: These ﬁrst real‐life data on BEGEV regimen as ﬁrst

salvage setting in HL showed a relevant rate of objective responses

and a limited myelotoxicity with no impairment of a subsequent

mobilization of peripheral blood stem cells.

Keywords: Hodgkin lymphoma, Therapeutics and Clinical Trials in

Lymphoma ‐ Other

No conﬂicts of interest pertinent to the abstract.

192 | CAMRELIZUMAB COMBINED WITH GEMOX IN

PATIENTS WITH RELAPSED OR REFRACTORY HODGKIN

LYMPHOMA

Y. Xie

, L. Mi

, W. Zheng

, L. Ping

, N. Lin

, M. Tu

, C. Zhang

, Z. Ying

W. Liu

, L. Deng

, M. Wu

, T. Du

, Y. Tang

, X. Wang

, J. Zhu

, Y. Song

Key laboratory of Carcinogenesis and Translational Research (Ministry of

Education), Peking University Cancer Hospital & Institute, Department of

lymphoma, beijing, China

Objective: PD‐1antibody has shown remarkable efﬁcacy in relapsed

or refractory Hodgkin lymphoma (R/R HL). Here we designed a

clinical trial to evaluate the efﬁcacy and safety of PD‐1 antibody

camrelizumab combined with GEMOX chemotherapy in R/R HL pa-

tients. The preliminary results had been obtained.

Method: This is an open‐label, single‐center, non‐randomized, phase

2 study (NCT04239170). The main inclusion criteria include age≥18,

ECOG < 2, histopathology conﬁrmed classical HL, number of previ-

ous chemotherapy regimen ≥1 but <3, having measurable lesion(s)

assessed by Lugano 2014 criteria and preparing to receive autolo-

gous stem cell transplantation (ASCT). The treatment schedule is

shown in Figure 1. The primary endpoint is the proportion of patients

who achieved PET‐CT‐conﬁrmed complete response (CR) according

to Lugano 2014 criteria.

Results: From March 2020 to February 2021, 14 patients were

enrolled. One patient was excluded because of the diagnosis of

diffused large B‐cell lymphoma in the second biopsy. The remaining

13 patients ranged in age from 22 to 48, with a male‐to‐female ratio

of 8:5. Among the 13 patients, nine patients failed to response in the

last treatment. Among the 4 relapsed cases, 2 of them recurred

within one year and 3 of them had extranodal invasion. At the ﬁrst

tumor response evaluation, 61.5% (8/13) patients achieved CR and

30.8% (4/13) patients achieved PR, resulting an ORR of 92.3%. Only

one patient had stable disease (SD). The 5 patients who had PR or SD

received an additional cycle of camrelizumab plus GEMOX treatment,

and 3 of them had a second tumor response results, in which one

patient who had PR in the ﬁrst evaluation was found to achieve CR.

The remaining 2 patients were still waiting for evaluation. Up to now,

collection of the autologous hematopoietic stem cells was completed

in seven patients and the average number of CD34+ cells was 2.24 �

/kg. Most adverse events (AEs) were of grade 1 to 2. No grade 4

or above AEs occurred. AEs of grade 3 included neutropenia (2.3%)

and transfusion reaction (2.3%).

Conclusion: The preliminary data obtained so far suggests that

camrelizumab combined with GEMOX chemotherapy has encour-

aging clinical efﬁcacy and tolerable toxicity in R/R HL patients and

merits continuous study.

Abbreviations: ASCT, autologous stem‐cell transplantation

*Patients who wait longer than 4 weeks to receive ASCT may be

considered to receive 1 or 2 camrelizumab monotherapy.

Keywords: Combination Therapies

No conﬂicts of interest pertinent to the abstract.

270

SUPPLEMENT ABSTRACTS

193 | HEALTH‐RELATED QUALITY OF LIFE AMONG PATIENTS

WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN

LYMPHOMA (R/R CHL) IN A PHASE 3 STUDY OF

PEMBROLIZUMAB VERSUS BRENTUXIMAB VEDOTIN

P. L. Zinzani

, M. Raut

, T. Saretsky

, R. Ramchandren

, A.

Santoro

, E. Paszkiewicz‐Kozik

, R. Gasiorowski

, N. A. Johnson

, J.

S. R. de Oliveira

, V. Buccheri

, G. F. Perini

, M. Dickinson

A. McDonald

, M. Ozcan

, N. Sekiguchi

, H. Giezek

, A.

Nahar

, J. Kuruvilla

IRCCS Azienda Ospedaliero–Universitaria di Bologna Istituto di Ema-

tologia “Seràgnoli”, and Dipartimento di Medicina Specialistica, Diag-

nostica e Sperimentale Università di Bologna, Specialized, Diagnostic and

Experimental Medicine, Bologna, Italy,

Merck & Co., Inc., Department of

Medical Oncology, Kenilworth, New Jersey, USA,

Merck & Co., Inc.,

Department of Medical Oncology, Kenilworth, New Jersey, USA,

University of Tennessee, Department of Mediciine, Knoxville, Tennessee,

USA,

Humanitas University and IRCCS Humanitas Research Center,

Department of Oncology, Milan, Italy,

Maria Sklodowska–Curie Na-

tional Institute of Oncology, Department of Medical Oncology, Warsaw,

Poland,

Concord Hospital, University of Sydney, Department of He-

matology, Sydney, Australia,

Jewish General Hospital, Department of

Hematology, Montreal, Canada,

Casa de Saúde Santa Marcelina,

Department of Medical Oncology, São Paulo, Brazil,

Hospital das

Clinicas da Faculdade de Medicina da Universidade de São Paulo,

Department of Clinical Medicine, São Paulo, Brazil,

Hospital Israelita

Albert Einstein, Department of Hematology, São Paulo, Brazil,

Peter

MacCallum Cancer Centre and Royal Melbourne Hospital, Department

of Lymphoma Disease, Melbourne, Australia,

Pretoria East Hospital,

Department of Hematology, Pretoria, South Africa,

Ankara University

School of Medicine, Department of Internal Medicine, Ankara, Turkey,

National Hospital Organization Disaster Medical Center, Department

of Medical Oncology, Tokyo, Japan,

Merck & Co., Inc., Department of

Medical Oncology, Kenilworth, New Jersey, USA,

Merck & Co., Inc.,

Department of Medical Oncology, Kenilworth, New Jersey, USA,

Princess Margaret Cancer Centre, Department of Medical Oncology

and Hematology, Toronto, Canada

Introduction: In the open‐label, international, randomized, phase 3

KEYNOTE‐204 study (NCT02684292), the PD‐1 inhibitor pem-

brolizumab (pembro) improved progression‐free survival vs bren-

tuximab vedotin (BV) in patients (pts) with R/R cHL who were

ineligible for or failed autologous stem cell transplant (ASCT). Here

we report analyses of exploratory end points of pembro vs BV on

health‐related quality of life (HRQoL) among R/R cHL pts from

KEYNOTE‐204.

Methods: Pts were randomized (1:1) to pembro 200 mg IV or BV

1.8 mg/kg IV Q3W. PRO analysis population included pts who

received ≥1 dose of study treatment and completed ≥1 PRO

assessment. European Organization for Research and Treatment of

Cancer (EORTC) QoL Questionnaire Core 30 (QLQ‐C30) was

administered at baseline, Q6W until wk 24, and Q12W thereafter.

Prespeciﬁed exploratory end points included least square mean

(LSM) change from baseline to wk 24 and time to deterioration

(TTD; ≥10‐point decline from baseline) for global health status/

QoL (GHS/QoL), functioning scales (physical, role, emotional,

cognitive, and social), symptom scales (fatigue, nausea/vomiting,

pain), and symptom single items (dyspnea, insomnia, appetite loss,

constipation, diarrhea, ﬁnancial difﬁculties). Differences between

groups were evaluated using two‐sided nominal P values not

controlled for multiplicity.

Results: Of 304 randomized pts, 296 (pembro, 146; BV, 150) were

in the PRO analysis. Compliance rates were >90% at baseline and

>80% at wk 24 in both groups. Higher scores on GHS/QoL and

functioning scales and lower scores on symptom scales indicate

better HRQoL. LSM change from baseline to wk 24 was higher

with pembro vs BV for the EORTC QLQ‐C30 GHS/QoL (7.29 vs –

1.31; LSM difference, 8.60; 95% CI, 3.89, 13.31; P = 0.0004)

physical (4.31 vs –1.93; LSM difference, 6.24; 95% CI, 1.87, 10.62;

P = 0.0054), role (6.86 vs –1.19; LSM difference, 8.04; 95% CI,

1.90, 14.19; P = 0.0105), and social (5.96 vs 0.54; LSM difference,

5.42; 95% CI, 95% CI, 0.18, 10.67; P = 0.0429) functioning scores.

No treatment differences in emotional and cognitive functioning

scores were observed. For symptom scales, LSM changes from

baseline to wk 24 were lower with pembro vs BV for the fatigue

(LSM difference, –11.88; 95% CI, –17.26, –6.50; P < 0.0001) and

FIGURE 1 Experiment design

SUPPLEMENT ABSTRACTS

271

pain (–6.03; –11.70, –0.36; P = 0.0371) scores; no treatment dif-

ferences for nausea/vomiting symptom scores were observed. LSM

change from baseline to wk 24 was lower with pembro vs BV in

all symptom single‐item scores except constipation and diarrhea

(Figure). Compared with BV, pembro prolonged TTD for EORTC

QLQ‐C30 GHS/QoL, physical, role, emotional, and social func-

tioning scales and for EORTC QLQ‐C30 fatigue and pain symptom

scales.

Conclusions: Pembro improved pt HRQoL compared with BV and

prolonged TTD. Findings further support pembro as the preferred

treatment option for pts with R/R cHL who are ineligible for or fail

ASCT.

The research was funded by: Merck Sharp & Dohme Corp., a sub-

sidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Keywords: Hodgkin lymphoma, Immunotherapy

Conﬂicts of interests pertinent to the abstract

P. L. Zinzani

Consultant or advisory role: Roche, Janssen, Takeda, Eusapharma,

Incyte, Beigene, Kirin Kyowa, Takeda, Merck, Bayer, Novartis

Honoraria: Servier, AbbVie, Merck, Eusapharma, Novartis, Incyte;

Takeda Beigene, Janssen, Roche, Bayer, Sanoﬁ, Kirin Kiowa

Other remuneration: Speaker bureau: Merck, Eusapharma, Takeda,

Novartis, Kirin Kiowa, Janssen, Roche, Incyte

M. Raut

Employment or leadership position: Merck & Co., Inc.

T. Saretsky

Employment or leadership position: Merck & Co., Inc.

Stock ownership: Merck & Co., Inc.

R. Ramchandren

Consultant or advisory role: Seattle Genetics

Research funding: Merck, Pharmacyclics, Beigene, BMS

A. Santoro

Consultant or advisory role: Bristol Myers Squibb, Servier, Gilead,

Pﬁzer, Eisai, Bayer, Merck Sharp & Dohme, Arqule, Sanoﬁ

Other remuneration: Speaker bureau: Takeda, Bristol Myers Squibb,

Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pﬁzer,

Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, Merck Sharp & Dohme

E. Paszkiewicz‐Kozik

Educational grants: Roche, Celgene, Takeda, AbbVie

R. Gasiorowski

Honoraria: MSD, AbbVie, Novartis, Astellas, Takeda

N. A. Johnson

Consultant or advisory role: Merck, BMS, Roche, Lundbeck, AbbVie,

Johnson and Johnson, Seattle Genetics

Honoraria: Merck, BMS, Roche, Lundbeck

V. Buccheri

Consultant or advisory role: AstraZeneca

Research funding: AstraZeneca, MSD, Takeda

Other remuneration: Speaker bureau: AstraZeneca

G. F. Perini

Consultant or advisory role: Janssen, AbbVie, Takeda, MSD,

AstraZeneca

Other remuneration: Speaker bureau: Janssen, AbbVie, Takeda, MSD,

AstraZeneca

M. Dickinson

Consultant or advisory role: Roche, MSD, Novartis, Gilead, Janssen

Honoraria: MSD, Roche, Amgen, Janssen, BMS, Novartis, Gilead

Research funding: MSD, Novartis, Roche, Takeda, Celgene

Other remuneration: Speaker bureau: Novartis

A. McDonald

Educational grants: Roche, Celgene, Takeda, AbbVie

LSM Changes From Baseline in EORTC QLQ‐C30 Symptom Single Item Scale at Week 24

272

SUPPLEMENT ABSTRACTS

M. Ozcan

Honoraria: Takeda, Amgen

Research funding: Janssen, Celgene, Takeda, Archigen, Roche, Bayer,

MSD, AbbVie, Novartis

Educational grants: BMS, Jazz, Roche, Sanoﬁ, Abdi İbrahim, Janssen,

Takeda, AbbVie, Amgen

N. Sekiguchi

Research funding: Ono, A2 Healthcare, Astellas, Janssen, Merck

Sharp & Dohme, Otsuka, Pﬁzer, PPD‐SNBL, Sumitomo Dainippon

Pharma, Daiichi Sankyo Company, Bristol Myers Squibb

H. Giezek

Employment or leadership position: Merck & Co., Inc.

A. Nahar

Employment or leadership position: Merck & Co., Inc.

J. Kuruvilla

Consultant or advisory role: AbbVie, BMS, Gilead, Karyopharm,

Merck, Roche, Seattle Genetics

Honoraria: Amgen, Antengene, Astra Zeneca, BMS, Gilead, Incyte,

Janssen, Karyopharm, Merck, Novartis, Pﬁzer, Roche, Seattle Ge-

netics, TG Therapeutics

Research funding: Canadian Cancer Society, Leukemia and Lym-

phoma Society Canada, Princess Margaret Cancer Foundation,

Janssen, Roche, AstraZeneca

Other remuneration: Data Safety Monitoring Board: Karyopharm

194 | REAL WORLD OUTCOMES AND RESPONSES TO

SECOND‐LINE THERAPY IN RELAPSED/REFRACTORY HODGKIN

LYMPHOMA: A MULTICENTRE UK STUDY

R. Shotton

, A. A. Kirkwood

, M. Northend

, D. Fathoala

, K. Burton

G. Ferguson

, L. Aiken

, C. Shrubsole

, L. Henry

, M. Owen

R. Oliver

, N. Martinez‐Calle

, A. Etherington

, E. Gallop‐Evans

C. Burton

, F. Miall

, W. Osborne

, R. Le Dieu

, P. McKay

K. Ardeshna

, G. P. Collins

, E. Phillips

The Christie NHS Foundation Trust, Medical oncology, Manchester, UK,

UCL Cancer institute, University College London, Cancer Research UK and

UCL Cancer Trials Centre, London, UK,

University College Hospital,

University College London, Haematology Dept, London, UK,

Oxford

University Hospitals NHS Foundation Trust, Haematology Dept, Oxford,

UK,

Beatson West of Scotland Cancer Centre, Haematology Dept,

Glasgow, UK,

Bart's Health NHS Trust, Haemato‐Oncology Dept, London,

UK,

Newcastle upon Tyne Hospitals NHS Foundation Trust, Haematology

Dept, Newcastle, UK,

University Hospitals of Leicester, Haematology Dept,

Leicester, UK,

Leeds Cancer Centre, , Leeds, UK,

University Hospitals

Bristol, Haematology Dept, Bristol, UK,

Nottingham University Hospitals,

Haematology Dept, Nottingham, UK,

Velindre Cancer Centre, Haema-

tology, Cardiff, UK,

Velindre Cancer Centre, Clinical Oncology, Cardiff,

UK,

The Christie NHS Foundation Trust, NIHR Manchester Biomedical

Research Centre and University of Manchester, Manchester, UK

Introduction: For patients (pts) with relapsed or refractory (R/R)

Hodgkin lymphoma (HL), the aim of second‐line (2L) treatment is to

achieve complete metabolic response (CMR) prior to high‐dose

chemotherapy and autologous stem cell transplant (ASCT). Inten-

sive chemotherapy is commonly used, but there is no standard of

care and CMR rates using contemporary ﬂuorodeoxyglucose‐

positron emission tomography (PET) assessment are unknown.

Novel agents have shown promise, but comparative data with con-

ventional 2L chemotherapy are lacking. We aimed to assess response

to 2L chemotherapy according to the Lugano classiﬁcation.

Methods: This retrospective study includes all pts with R/R HL who

received intensive 2L chemotherapy with intent to consolidate with

ASCT at 11 UK centres between 01/01/2015 and 31/12/2019. PET

response was locally assessed using Deauville criteria (DS). CMR was

deﬁned as a DS of 1‐3. Survival was measured from start of 2L

treatment.

Results: 252 pts were included: 58% were male and median age at 2L

treatment was 32y (range 16‐70). 87% had received ABVD as initial

frontline (1L) treatment. 44% had refractory disease, 20% had early

relapse (3‐12m from end of 1L) and 36% late relapse. Extranodal

disease was present in 46%, B symptoms in 30% and anaemia in 15%

(haemoglobin (Hb) < 120/< 105 g/L for men/women).

The most common 2L regimens were ESHAP (N = 95, 38%), GDP/

GEM‐P (N = 61, 24%), IGEV (N = 50, 20%) and IVE (N = 29, 12%),

primarily determined by centre preference. Treatment was changed

due to toxicity in 9 pts (4%). There were no treatment‐related deaths.

In total, 49% achieved CMR, 27% partial response, 7% stable disease

and 18% progressive disease. CMR rates were 40% with ESHAP, 54%

with GDP/GEM‐P, 54% with IGEV, 55% with IVE and 30% with other

intensive regimens (N = 17). In pts with refractory disease, 36% had

CMR, vs 47% for early relapse and 60% for late relapse. In multi-

variable analysis, CMR was signiﬁcantly associated with late vs early

relapse or refractory disease (odds ratio (OR) 2.32 (1.30 – 4.13), p =

0.004). There was a trend towards lower CMR rates for pts with

anaemia (OR 0.49 (0.22 – 1.09), p = 0.08). There was no association

with choice of 2L regimen.

Median follow‐up was 28 months. In total, 121 pts (48%) received

SCT after 2L treatment (120 ASCT; 1 allogeneic), of which 104

(86%) had CMR pre‐ASCT. 2 pts with CMR failed stem cell harvest.

Median progression‐free survival (PFS) for all pts was 35 months

(Figure). 2‐year PFS and overall survival rates were 54% and 87%,

respectively. For pts with CMR after 2L who received ASCT, 2‐year

PFS was 79%.

Conclusions: In this large cohort of pts with R/R HL, CMR rates after

2L treatment were strongly associated with duration of response to

1L treatment, but not choice of 2L chemotherapy. Outpatient regi-

mens such as GDP had similar efﬁcacy to inpatient regimens. CMR

and ASCT rates were suboptimal, highlighting a need to evaluate

novel regimens in this setting.

Keywords: Hodgkin lymphoma, Chemotherapy, Stem Cell

Transplant

No conﬂicts of interest pertinent to the abstract.

SUPPLEMENT ABSTRACTS

273

195 | CLINICAL OUTCOMES OF RELAPSED HODGKIN

LYMPHOMA PATIENTS AFTER CONTEMPORARY FIRST‐LINE

TREATMENT: RESULTS FROM THE GERMAN HODGKIN STUDY

GROUP

P. J. Bröckelmann

, H. Müller

, S. Gillessen

, X. Yang

, L. Koeppel

V. Pilz

, P. Marinello

, P. Kaskel

, M. Raut

, M. Fuchs

P. Borchmann

, A. Engert

, B. von Tresckow

Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO

ABCD), University of Cologne, Department I of Internal Medicine and

German Hodgkin Study Group (GHSG), Cologne, Germany,

Merck & Co.,

Inc., Kenilworth, USA,

MSD Sharp & Dohme, GmbH, Haar, Germany,

University Hospital Essen, University of Duisburg‐Essen, Department of

Hematology and Stem Cell Transplantation, West German Cancer Center,

Essen, Germany

Introduction: The relative beneﬁt of targeted agents increasingly

investigated and applied in relapsed or refractory Hodgkin

lymphoma (rrHL) is difﬁcult to estimate due to a lack of ran-

domized trials. This retrospective study hence aimed to evaluate

disease characteristics, treatment patterns and associated out-

comes at ﬁrst occurrence of rrHL after contemporary ﬁrst‐line

treatment.

Methods: We retrospectively identiﬁed patients with sufﬁciently

documented ﬁrst rrHL initially receiving standard of care 1

‐

line treatment in the GHSG HD13 (early‐stage favorable), HD14

(early‐stage unfavorable) and HD15 (advanced‐stage) trials. We

additionally evaluated rrHL patients enrolled in the placebo‐

controlled randomized GHSG HDR3i trial comparing conventional

DHAP vs. everolimus + DHAP salvage therapy prior planned

autologous stem‐cell transplantation (ASCT). We assessed overall

survival (OS) starting with date of 1

rrHL and ending with date of

death for any reason and progression free survival (PFS) measured

from date of rrHL to second rrHL or death from any reason. Pa-

tient, disease and treatment characteristics were analyzed with

descriptive statistics and survival endpoints with Kaplan‐Meier

estimates.

Results: A total of 437 patients with ﬁrst rrHL (HD13: n = 87, HD14:

n = 118, HD15: n = 188, HDR3i: n = 44) were identiﬁed. Of these

402 with sufﬁcient documentation and follow‐up were assessed with

a median age of 37.5 years (18.4‐76.8). Time to relapse was ≤12

months in 49% and stage III/IV rrHL present in 52% of patients. High‐

dose chemotherapy and autologous stem‐cell transplantation (ASCT)

with and without consolidation was administered in 20% and 52% of

patients, respectively. The remaining 111 patients (27%) did not

receive ASCT mostly due to insufﬁcient response to salvage

chemotherapy, advanced age, localized disease or patients’ prefer-

ence. Overall, 10‐year PFS and OS after ﬁrst relapse were 48.2%

(95% conﬁdence interval CI: 42.0%‐54.4%) and 59.3% (95%CI:

53.2%‐65.4%), respectively (Figure 1). Patients unsuitable for ASCT

had less favorable 10‐year PFS (32.5%, 95%CI: 19.1%‐45.9%) and OS

(41.9%, 95%CI: 28.1%‐55.6%). Signiﬁcantly inferior PFS and OS was

also observed in primary refractory patients (10‐year PFS 36.0%,

95%CI: 24.2%‐47.9%; 10‐year OS 44.5%, 95%CI: 31.6%‐56.6%) and

those with stage IV disease at rrHL (10‐year PFS 29.3%, 95%CI:

18.5%‐40.9%; 10‐year OS 39.6%, 95%CI: 27.9%‐51.1%). Outcomes in

these higher risk patients appeared more favorable with ASCT than

without ASCT.

Conclusions: Our analysis of relapse and treatment patterns after

contemporary HL therapy provides a robust benchmark to evaluate

novel therapeutic strategies in rrHL. We conﬁrm the curative po-

tential of current rrHL treatments including non‐ASCT approaches

and roughly 50% of rrHL patients do not experience a consecutive

relapse after 2

‐line treatment.

EA – previously submitted to EHA 2021.

The research was funded by: Merck Sharp & Dohme Corp., Kenil-

worth, NJ, USA

Keywords: Hodgkinlymphoma, Chemotherapy, StemCellTransplant

Conﬂicts of interests pertinent to the abstract

X. Yang

Employment or leadership position: Merck Sharp & Dohme Corp., USA

Stock ownership: MERCK & CO., INC.

PFS all patients (A), PFS all patients receiving an SCT after 2L theraphy (B)

274

SUPPLEMENT ABSTRACTS

L. Koeppel

Employment or leadership position: MSD Sharp & Dohme GmbH,

Germany

V. Pilz

Employment or leadership position: MSD Sharp & Dohme GmbH,

Germany

P. Marinello

Employment or leadership position: MSD Sharp & Dohme Corp., USA

Stock ownership: MERCK & CO., INC.

P. Kaskel

Employment or leadership position: MSD Sharp & Dohme GmbH,

Germany

Stock ownership: MERCK & CO., INC.

M. Raut

Employment or leadership position: MSD Sharp & Dohme Corp., USA

Stock ownership: MERCK & CO., INC.

B. von Tresckow

Research funding: Merck Sharp & Dohme

FIGURE 1 PFS (panel A) and OS (B) after rrHL in patients treated in HD13, HD14, HD15, HDR3i

SUPPLEMENT ABSTRACTS

275

196 | PET‐ADAPTED THERAPY AFTER THREE CYCLES OF

ABVD FOR ALL STAGES OF HODGKIN LYMPHOMA: LONG TERM

FOLLOW UP OF THE GATLA LH‐05 TRIAL

A. Pavlovsky

, L. Fiad

, I. Fernandez

, V. Prates

, N. Kurgansky

A. Cerutti

, F. Sackman

, F. Negri

, L. Zoppegno

, P. Negri

G. Remaggi

, L. Ferrari

, R. Mariano

, L. Guanchiale

, J. Maradei

S. Rudoy

, F. Giuliani

, E. Roveri

, A. Enrico

, S. Zabaljauregui

M. Cabrejo

, C. Gumpel

, A. Quartara

, C. M. Gonzalez

A. Varela

, M. Riddick

, S. Pavlovsky

Fundaleu, Hematology, Buenos Aires, Argentina,

Hospital Italiano La

Plata, Hematology, Buenos Aires, Argentina,

Clínica Doctus, Hematology,

Santa Fe, Argentina,

IDHEA Clínica Hematológica, Hematology, Rosario,

Santa Fe, Argentina,

Instituto Privado de Hematología y Hemoterapia,

Hematology, Paraná, Entre Ríos, Argentina,

HIGA General José de San

Martín La Plata, Hematology, Buenos Aires, Argentina,

Hospital San

Martín, Hematology, Paraná, Entre Ríos, California, Argentina,

Hospital

Universitario Privado de Córdoba, Hematology, Córdoba, Argentina,

Hospital Municipal Dr. E. Ferreyra, Hematology, Necochea, Buenos Aires,

Argentina,

Clínica Modelo de Morón, Hematology, Buenos Aires,

Argentina,

Hospital Provincial del Centenario, Hematology, Rosario,

Santa Fe, Argentina,

Hospital Italiano La PLata, Hematology, Buenos

Aires, Argentina,

Instituto de Investigaciones Hematológicas Mariano R.

Castex, Hematology, Buenos Aires, Argentina,

Sanatorio Municipal Julio

Méndez, Hematology, Buenos Aires, Argentina,

Sanatorio Plaza,

Hematology, Rosario, Santa Fe, Argentina,

Hospital Provincial del

Centenario, Hematology, Rosario, Santa Fe, Argentina,

Sanatorio Las

Lomas, Hematology, Buenos Aires, Argentina,

Departamento de

Matematicas‐Facultad de Ciencias Exactas‐ UNLP‐CONICET, Mathe-

matics, Buenos Aires, Argentina,

Fundaleu, Hematology, Buenos Aires,

Argentina

PET CT adapted treatment for ﬁrst line Hodgkin Lymphoma has been

widely studied in the last decades. Long‐term follow‐up is important

to judge both efﬁcacy and safety of this approach.

Patients and Methods: We analyzed updated follow‐up data on all

patients (pts.) treated within the LH‐05 GATLA trial. Newly diag-

nosed pts. with HL Stages I‐IV were included. All patients received 3

ABVD and were evaluated with a PET‐CT (PET‐CT+3). Pts. with a

negative PET‐CT+3 (DS 1 and 2) were considered in metabolic CR

and received no further therapy. Pts with DS 3 and 4 completed 6

ABVD and IFRT on PET‐CT positive areas. Pts with progressive dis-

ease (DS 5) after 3 ABVD received salvage chemotherapy. With a

median age of 35 yrs., 300 presented with localized stage and 190

with advanced stage.

Results: In LH‐05 of all pts. 338 (69%) achieved CR with negative

PET‐CT+3, 152 (31 %) were PET‐CT+3 positive. With a median

follow up of 120 months the EFS and OS for all pts. at 5 years is 79.2%

and 94.3% respectively. Pts with negative PET‐CT+3 had an EFS of

89% and 80% for localized and advanced stage, compared to 63% for

276

SUPPLEMENT ABSTRACTS

all pts. with positive PET‐CT+3 (p < 0.0001). We perform a multi-

variate analysis for EFS which included age, stage, IPS, bulky disease,

extranodal areas and the result of the PET+3. This last parameter

together with age were the only ones with statistical signiﬁcance (p =

0.001 and 0.046 respectively). Stage at diagnosis was not signiﬁcant.

With long term follow up the OS at 5 years is 97.3% and 87.3% for all

PET+3 negative vs PET+3 positive pts.

When comparing the results LH‐05 with our previous clinical trial

(LH‐96) there is no difference in EFS and OS at 5 years but in LH‐05

only 31% received more than 3 cycles of ABVD and IFRT compared

to 61% and 100% in LH‐96. This PET adapted approach reduces

exposure to chemo and radiotherapy with no negative effect on long

term outcome.

Conclusion: This long term follow up data support the PET‐CT

adapted approach for all stages of HL after a short course of

ABVD. In the Cox regression model, PET‐CT at completion of

treatment was the most signiﬁcant factor associated to EFS.

Treatment with 3 cycles of ABVD can be adequate for pts. with

negative PET‐CT+3 regardless their stage at diagnosis. Nevertheless,

this long term follow up demonstrated that there is still room for

improvement trying to identify PET‐CT+3 negative patients that will

relapse and escalating treatment in PET‐CT+3 positive patients to

improve outcome. GATLA is designing a trial with the aim to improve

these two different risk groups.

Keywords: Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

197 | MODIFICATION OF ESCALATED BEACOPP WITH

DACARBAZINE SUBSTITUTION REDUCES TOXICITY WHILE

MAINTAINING EFFICACY FOR THE TREATMENT OF ADVANCED

STAGE HODGKIN LYMPHOMA

A. Santarsieri

, K. Sturgess

, P. Brice

, T. F. Menne

, W. Osborne

, T.

Creasey

, K. M. Ardeshna

, S. Behan

, K. Bhuller

, S. Booth

, G. P.

Collins

, K. Cwynarski

, M. Furtado

, S. Iyengar

, S. G. Jones

, D.

O'Mahony

, N. Martinez‐Calle

, P. McKay

, S. K. Nagumantry

, J.

F. Rudge

, N. Shah

, G. Stafford

, A. Sternberg

, B. J. Uttenthal

, A.

K. McMillan

, G. A. Follows

Cambridge University Hospitals NHS Foundation Trust, Haematology,

Cambridge, UK,

Hôpital Saint‐Louis, Hématologie‐Oncologie, Paris,

France,

Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foun-

dation Trust, Haematology, Newcastle, UK,

Newcastle University Hos-

pitals NHSFT, Haematology, Newcastle, UK,

University College London

Hospitals NHS Foundation Trust, Haematology, London, UK,

University

Hospitals of Leicester NHS Trust, Haematology, Leicester, UK,

Oxford

University Hospitals NHS Foundation Trust, Haematology, Oxford, UK,

Royal Cornwall Hospitals NHS Trust, Haematology, Cornwall, UK,

The

Royal Marsden NHS Foundation Trust, Haematology, London, UK,

Sherwood Forest Hospitals NHS Foundation Trust, Haematology, Not-

tinghamshire, UK,

Cork University Hospital, Oncology, Cork, Ireland,

Nottingham University Hospitals NHS Trust, Haematology, Nottingham,

UK,

Beatson West of Scotland Cancer Centre, Haematology, Glasgow,

UK,

Peterborough City Hospital, North West Anglia NHS Foundation

Trust, Haematology, Peterborough, UK,

Bullard Laboratories, University

of Cambridge, Cambridge, UK,

Norfolk and Norwich University Hospi-

tals NHS Foundation Trust, Haematology, Cambridge, UK,

Great

Western Hospitals NHS Foundation Trust, Haematology, Swindon, UK

In the treatment of advanced Hodgkin lymphoma, it is increasingly

common practice to modify escalated BEACOPP (eBPP) by removing

oral procarbazine and replacing it with IV dacarbazine (250mg/m2

D2‐3) to reduce haematopoietic stem cell and gonadal toxicity.

However, published data of the “escalated BEACOPDac (eBPDac)”

regimen are limited.

From 2009, 205 patients were treated ﬁrst line with either eBPP (n

= 58) at 4 UK centres, or eBPDac (n = 147) at 16 centres in the UK,

Ireland and France with median follow up 51.3 months and 22.9

months respectively. Patients were well matched with no signiﬁcant

differences in age (median: 23 y vs 27 y), sex, stage (stage 3/4: 81%

vs 83%) and IPS (IPS3+: 74% vs 65%). 51% of eBPDac patients

received only 4 cycles (vs 12% eBPP patients; p < 0.001) reﬂecting

publication of HD18 trial data. In total, 74% patients achieved

iPET2 Deauville score ≤3 and 90% achieved PET negative remission

by end of treatment. 77% of eBPDac patients achieved iPET2

Deauville ≤3 which was statistically similar to the eBPP cohort

(67%; p = 0.181) and matched the 76% iPET D2/3 reported in

HD18. Of 205 patients, 202 are alive and 197 continue in ﬁrst

remission. Two eBPP patients have relapsed at 13 and 41 months

and the latter died of refractory disease. One eBPDac patient had

primary refractory disease, and three have relapsed at 2, 7 and 24

months. One 56‐year‐old eBPDac patient with high IPS died of

bowel perforation during cycle 1 and one 34‐year‐old with alcoholic

liver disease died 8 months after treatment while in remission.

Toxicity was compared over the ﬁrst 4 cycles. Mean day 8 (D8) ALT

was similar between the two regimens. Mean D8 neutrophil count

was lower in eBPDac than eBPP patients (1.81 vs 2.45; p = 0.067; G‐

CSF given D9), however it increased to 5.61 in eBPDac patients

given GCSF from D4. There is a trend toward fewer non‐elective

days of inpatient care for eBPDac compared with eBPP (mean 3.74

vs 5.83; p = 0.118), and eBPDac patients received fewer red cell

transfusions compared with eBPP patients (mean 1.93 units vs 4.16

units; p < 0.001). Women aged <35, who completed ≥4 cycles of

eBPDac/eBPP had a similar rate of return of menstrual cycles (eBPP

22/25; eBPDac 29/29), although eBPDac patients appeared to

restart menstruation earlier post chemotherapy (mean 4.48 months

vs 9.12 months, p = 0.0026). However, this could also reﬂect the

higher mean chemotherapy cycle number completed by the eBPP

women (5.86 vs 4.60; p < 0.001). The use of Goserelin varied be-

tween centres.

Accepting the limitations of a retrospective study, we suggest that

substituting dacarbazine for procarbazine is unlikely to compromise

the efﬁcacy of eBPP and may have some toxicity beneﬁts. Despite a

predominance of high risk advanced stage patients, with nearly 2

years median follow up we have observed only 2 deaths and 4

SUPPLEMENT ABSTRACTS

277

progression events from 147 patients treated with eBPDac, sug-

gesting this regimen is highly efﬁcacious in Hodgkin lymphoma.

EA – previously submitted to regional or national meetings (up to

1000 attendees) and EHA 2021.

Keywords: Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

A. Santarsieri

Honoraria: Janssen

P. Brice

Other remuneration: Takeda France, Millenium Takeda, BMS

T. F. Menne

Other remuneration: Kite/Gilead, Amgen, Novartis, Celgene, Daiichi

Sankyo, Takeda, Roche, Janssen, Astra Zeneca, Jazz, Pﬁzer, Bayer,

Kyowa Kirin

W. Osborne

Other remuneration: Roche, Takeda, Pﬁzer, Servier, Gilead, MSD,

Novartis

K. M. Ardeshna

Other remuneration: Gilead, Celgene

G. P. Collins

Other remuneration: Gilead

K. Cwynarski

Other remuneration: Adienne, Takeda, Roche, Autolus, KITE, Gilead,

Celgene, Atara, Janssen

M. Furtado

Educational grants: Abbvie

S. Iyengar

Other remuneration: Takeda, Janssen, Gilead, Abbvie, Roche

N. Martinez‐Calle

Other remuneration: Abbvie

P. McKay

Other remuneration: Epizyme

S. K. Nagumantry

Other remuneration: Takeda, Alexion, Abbvie

N. Shah

Other remuneration: Abbvie

B. J. Uttenthal

Other remuneration: Roche, Takeda, Jazz

278

SUPPLEMENT ABSTRACTS

A. K. McMillan

Other remuneration: Pﬁzer, F Hoffman‐La Roche Ltd, BMS, Celgene,

Novartis, Gilead, Sandoz, MSD

G. A. Follows

Other remuneration: Janssen, Abbvie, Roche, Astra Zeneca

198 | MATURE RESULTS FROM A PHASE II TRIAL OF

BRENTUXIMAB VEDOTIN PLUS ADRIAMYCIN AND

DACARBAZINE WITHOUT RADIATION IN NON‐BULKY LIMITED

STAGE CLASSICAL HODGKIN LYMPHOMA

J. S. Abramson

, E. M. Bengston

, R. Redd

, J. A. Barnes

T. Takvorian

, L. Sokol

, F. Lansigan

, P. Armand

, B. Shah

E. Jacobsen

, R. Martignetti

, E. Turba

, S. R. Metzler

, V. Patterson

A. S. LaCasce

, C. M. Bello

Massachusetts General Hospital, Center for Lymphoma, Boston,

Massachusetts, USA,

Dartmouth‐Hitchcock Medical Center, Hematology/

Oncology, Lebanon, New Hampshire, USA,

Dana‐Farber Cancer Institute,

Biostatistics, Boston, Massachusetts, USA,

Mofﬁtt Cancer Center, He-

matology/Oncology, Tampa, USA,

Dana‐Farber Cancer Institute, Medical

Oncology, Boston, USA

Background: ABVD with or without radiation is standard therapy for

limited stage classical Hodgkin lymphoma (HL), but carries risks of

bleomycin lung injury and radiation toxicity. We previously combined

brentuximab vedotin (BV) with AVD in limited stage HL which

resulted in a high CR rate, but at the cost of increased neutropenic

fever and neuropathy, likely due to overlapping toxicity with BV and

vinblastine; similar ﬁndings were observed with BV‐AVD in advanced

stage HL. We therefore evaluated BV plus AD in non‐bulky stage I‐II

HL.

Methods: This is a multicenter single arm phase 2 study. Patients (pts)

received BV 1.2 mg/kg plus standard adriamycin and dacarbazine on

days 1 and 15 of each 28 day cycle. Prophylactic GCSF was not

included. Patients received 4 or 6 cycles based on interim PETCT

performed following cycle 2 (PET‐ pts, deﬁned as Deauville 1‐3,

received 4 cycles, PET+ pts received 6 cycles). Radiation was not

allowed for patients in end of treatment (EOT) CR. The primary

endpoint was complete response rate (CRR) at EOT. A sample size of 34

was required to detect an end of treatment CRR of 95% (compared to

null hypothesis 81%) with 91% power and alpha error of 0.09.

Results: 34 pts were enrolled. Median age was 36 (range 18‐63).

Stage was IA (3), IB (1), IIA (29) and IIB (1). Risk per the GHSG criteria

was early favorable in 18 (53%) and unfavorable in 16 (47%). The

interim CR rate was 94%; 32 pts received 4 total cycles and 2

received 6 cycles. No pts received consolidative radiation. The pri-

mary endpoint of EOT CRR was 97% (33/34 pts). With a median

follow‐up of 46 months, 31/34 patients remain progression‐free; the

estimated 4‐year PFS and OS are 88% (95% CI 65,96) and 100%

(95% CI 100,100), respectively. No events have been reported after

30 months. There were no differences in CRR or PFS between early

favorable and unfavorable pts. The most common adverse events of

any grade were nausea (85%), peripheral sensory neuropathy (59%),

fatigue (56%), constipation (41%), alopecia (38%) and neutropenia

(24%). Most toxicities were low grade, with only 5 patients (15%)

experiencing any grade 3 toxicity, and there were no grade 4 or 5

toxicities. Speciﬁcally, 2 pts had grade 3 neutropenia, and all other

grade 3 toxicities occurred in 1 pt each. Peripheral neuropathy was

grade 1 in 17 pts and grade 2 in 2 pts. There were no cases of grade 4

neutropenia, and no cases of neutropenic fever.

Conclusions: BV‐AD for 4‐6 cycles appears highly effective and well

tolerated in both early favorable and early unfavorable non‐bulky

limited stage classical HL. Most pts required 4 total cycles. Toxicity

is predominantly low grade and notable for a low incidence of neu-

tropenia, alopecia, and moderate‐severe peripheral neuropathy. This

promising regimen avoids bleomycin, vinblastine, radiation and pro-

phylactic GCSF. A phase II trial using this regimen plus nivolumab in

limited stage HL is currently enrolling (ClinicalTrials.gov

NCT03646123).

The research was funded by: Seattle Genetics

Keywords: Hodgkin lymphoma, Chemotherapy, Combination

Therapies

No conﬂicts of interest pertinent to the abstract.

SUPPLEMENT ABSTRACTS

279

199 | BRENTUXIMAB VEDOTIN AS CONSOLIDATION

TREATMENT IN PATIENTS WITH STAGE I/II CLASSICAL

HODGKIN'S LYMPHOMA AND A POSITIVE FDG‐PET AFTER 2

CYCLES OF ABVD: A LYSA PHASE 2 STUDY

T. Gastinne

, K. Bouabdallah

, H. Moatti

, B. Tessoulin

, J. M. Shiano

del colella

, T. Lamy

, O. Casasnovas

, C. Borel

, A. Stamatoullas

A. C. Gac

, D. Chaoui

, P. Feugier

, A. Delmer

, C. Bonnet

, Luc‐

M. Fornecker

, J. Lazarovici

, F. Le Bras

, H. Ghesquieres

M. Meignan

, A. Traverse Glehen

, P. Brice

University Hospital of Nantes, Hematology, Nantes, France,

Hopital

Haut‐Levêque, Centre Hospitalier Regional Universitaire de Bordeaux,

Department of Hematology, Pessac, France,

Hôpital saint Louis APHP,

Université Paris 7, Department of Oncohaematology, Paris, France,

Institut Paoli‐Calmettes, Aix‐Marseille Université, Haematology Depart-

ment, Marseille, France,

Rennes University Hospital, Department of

Clinical Hematology, MICA Research Unit, Rennes, France,

University

Hospital F Mitterrand and INSERM 1231, Department of Haematology,

Dijon, France,

IUCT‐Oncopole, CHU Toulouse, Department of Haema-

tology, Toulouse, France,

Centre Henri Becquerel, Department of

FIGURE 1

280

SUPPLEMENT ABSTRACTS

Haematology, U918, Rouen, France,

Centre Hospitalier Universitaire de

Caen, Institut d'hématologie de Basse‐Normandie , Caen, France,

Centre

Hospitalier d'Argenteuil, Department of Hematology, Argenteuil, France,

Nancy University Hospital, Department of Clinical Hematology, INSERM

1256, Nancy, France,

University Hospital of Reims, Department of

Haematology, Reims, France,

CHU Liège, Liège Université, Campus

Universitaire de Sart Tilman, Clinical Hematology Unit, Liège, Belgium,

Strasbourg University Hospital, Department of Clinical Hematology,

Strasbourg, France,

Institut Gustave Roussy, Département des In-

novations Thérapeutiques et Essais Précoces, Villejuif, France,

CHU

Henri Mondor, Department of Hematology, Creteil, France,

Hospices

Civils de Lyon, Centre Hospitalier Lyon‐Sud and Université Claude Ber-

nard Lyon‐1, Department of Haematology, Lyon, France,

Hôpital H

Mondor, LYSA Imaging, Creteil, France,

Centre Hospitalier Lyon‐Sud,

Hospices Civils de Lyon, Pathology Department, cedex, France, Lyon,

France

Brentuximab vedotin (BV) as consolidation treatment in patients with

stage I/II classical Hodgkin's lymphoma and a positive FDG‐PET after

2 cycles (PET‐2) of ABVD: a LYSA phase 2 study.

Introduction: Early‐stage classical Hodgkin lymphoma (cHL) is highly

curable with chemotherapy and radiotherapy (RT). However, patients

with positive interim PET‐2 have poorer prognosis and require

treatment intensiﬁcation. Indeed, the H10 trial (André et al., 2017)

showed that escalated BEACOPP (BEACOPPesc) plus RT improves

5‐year PFS in PET‐2 positive patients treated with ABVD. The main

objective of the present study (NCT02298283) was to investigate the

beneﬁt of a consolidation with Brentuximab vedotin (BV) in newly

diagnosed early stage HL patients with insufﬁcient response ac-

cording to TEP after 2 cycles.

Patients and methods: The BRAPP2 trial is a multicentric, open‐label,

single arm phase II trial. All Patients aged from 18 to 65 years, with

an Ann Arbor clinical stage I or II cHL, PET‐2 Deauville score 4 & 5

after 2 courses of ABVD and without progressive disease were

eligible for the study. After inclusion, patients received 2 courses of

BEACOPPesc (so‐called induction) followed unless disease progres-

sion, by 30 Gy IFRT and then BV consolidation. BV (1.8 mg/kg) was

started at least 4 weeks and up to 6 weeks after RT and was given

every 3 weeks for 8 cycles. The BRAPP2 was designed to detect an

improvement of PFS at 2 years from 70% (null hypothesis) to 85%

(alternative hypothesis) assuming an 80% power at a 2‐sided alpha

(type I error) of 5%.

Results: From 04/2015 to 04/2018, 48 patients were included of

whom 41 patients started BV consolidation (efﬁcacy and safety set),

and 35 received the full 8 cycles of BV (Figure 1). A total of 56

adverse events (AEs) were reported during the study in 26 patients

(63.4%). Most frequent AEs were neurological with 12 patients

(29.3%) having experienced a grade ≥2 peripheral neuropathy, all

related to BV and leading to treatment discontinuation in 2 cases.

Febrile neutropenia occurred in 12.2% of patients, and was reported

during induction period. No fatal AEs were reported. According to

Cheson 2007 criteria, 34 patients (87.2%, 95%CI [72.6%; 95.7%])

achieved CR, evaluated after complete treatment for 85% patients.

With a median follow‐up duration of 3.1 years (95%CI = [2.6; 3.3]), 4

out of 41 (9.8%) patients progressed. The 2‐year PFS was 90.0%

(95%CI [75.5%; 96.1%]). One patient died, due to progression

(aggressive B‐cell lymphoma). The 2‐year OS was 97.5% (95%CI

[83.5%; 99.6%]). According to statistical study design, the null hy-

pothesis is rejected.

Conclusion: BEACOPPesc plus RT followed by BV consolidation for

PET‐2 positive early stage cHL provides high CR rate and prolonged

PFS with limited and manageable toxicities. BV consolidation is thus

an attractive option in this group of patients while there is still a

room for improvement to reduce progression during the induction

phase.

Keywords: Hodgkin lymphoma, Therapeutics and Clinical Trials in

Lymphoma ‐ Other

Conﬂicts of interests pertinent to the abstract

T. Gastinne

Consultant or advisory role: Gilead, Janssen, Takeda

Educational grants: Gilead, Roche

200 | OUTCOMES AFTER INITIAL REFUSAL OF CURATIVE

TREATMENT IN PATIENTS WITH HODGKIN LYMPHOMA IN

BRITISH COLUMBIA

M. Chahal

, A. Jiang

, A. Hayden

, K. Savage

, D. Villa

, D. Scott

A. Gerrie

, A. Lo

, M. Chan

, T. Pickles

, J. Connors

, L. Sehn

C. Freeman

BC Cancer, Medical Oncology, Vancouver, Canada,

British Columbia

Cancer Research Centre, Biostatistics, Vancouver, Canada,

BC Cancer,

Medical Oncology, Surrey , Canada,

BC Cancer, Centre for Lymphoid

Cancer and Division of Medical Oncology, Vancouver, Canada,

Cancer, Division of Radiation Oncology, Vancouver, Canada

Background: Classical Hodgkin lymphoma (cHL) is considered a

highly curable cancer. With standard combination chemotherapy

regimens, long‐term survival exceeds 95% for limited‐stage and 85%

for advanced‐stage patients. Despite these excellent outcomes some

patients delay or decline conventional treatment for cHL. We

retrospectively assessed the impact of initial treatment refusal on

outcomes of patients with cHL in British Columbia (BC).

Methods: Using the BC Cancer Lymphoid Cancer Database, we

identiﬁed all patients aged 18‐70 diagnosed between 1

Jan 1999‐

Dec 2020 that had documented treatment refusal at initial

presentation (‘refusers’ deﬁned as not receiving or delaying treat-

ment >16 weeks). We identiﬁed a control cohort (min. 3 controls/

refuser) treated within 8 weeks of diagnosis, matched for age, stage,

diagnosis date within 3 years, and blinded for outcome. All patients

had centrally reviewed biopsies and were treated with ABVD or

ABVD‐like regimens +/‐ radiotherapy if appropriate. Patient and

disease characteristics at baseline and at time of treatment were

analyzed with Chi‐squared test and one‐way ANOVA test. The

Kaplan‐Meier method was used to assess progression‐free survival

SUPPLEMENT ABSTRACTS

281

(PFS) and overall survival (OS), and statistical signiﬁcance between

groups was determined using the log‐rank test.

Results: We identiﬁed a cohort of 15 patients who initially refused

treatment and 47 matched controls. The control cohort was well‐

matched, with no statistically signiﬁcant differences in baseline char-

acteristics (age, sex, Ann Arbor stage, B symptoms, International

Prognostic Score (IPS) score, ECOG PS, and disease bulk) between

groups. The most common reason for initial treatment refusal was to

pursue alternative therapy (73%). 13 of 15 refusers eventually

accepted treatment (mean time to treatment 76 weeks [range 26‐214]

vs. 5 weeks [range 1‐8] for controls, p < 0.001). At time of treatment,

the proportion of refusers with advanced‐stage disease increased from

20% to 62% (p = 0.03) and had an associated alteration of treatment

plan, and 62% of patients developed higher risk disease with increased

IPS score (p = 0.02). At median follow‐up of 5 years (0.4‐21 years) for

all living patients, estimated 5‐year PFS was 65% vs 84%, and 5‐year

OS was 93% vs 98% for refusers and controls respectively. With

extended follow up, 13% of refusers (1 late death at 8 years) compared

to only 4% of controls died of cHL speciﬁcally.

Conclusions: This study highlights the impact of treatment refusal in

this highly curable malignancy. Initial refusal of treatment is associ-

ated with progression of stage, worsening prognostic score, escala-

tion to more prolonged treatment than required at diagnosis, and

increased risk of death from cHL. This analysis may help to provide

guidance to counselling physicians, as well as inform patients who

may be considering alternatives to standard of care for cHL.

EA – previously submitted to ASCO 2021.

Keywords: Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

K. Savage

Consultant or advisory role: Seattle Genetics, Bristol‐Myers Squibb,

Merck, Servier, Abbvie, Gilead Sciences, AstraZeneca

Honoraria: Seattle Genetics, Bristol‐Myers Squibb, Merck, Abbvie,

Gilead Sciences, AstraZeneca, Kyowa Kirin, Novartis, Novartis Can-

ada Pharmaceuticals Inc

Research funding: Roche, Bristol‐Myers Squibb

Educational grants: Seattle Genetics

Other remuneration: Beigene

D. Villa

Consultant or advisory role: Roche, Janssen, Lundbeck Canada,

Seattle Genetics, Gilead Sciences, Acerta Pharma/AstraZeneca, Cel-

gene, Abbvie, NanoString Technologies

Honoraria: Roche, Janssen, Lundbeck Canada, Seattle Genetics,

Gilead Sciences, Acerta Pharma/AstraZeneca, Celgene, Merck,

NanoString Technologies, Abbvie

Research funding: Roche

Educational grants: Roche, Janssen, Ludbeck Canada, Acerta Pharma

D. Scott

Consultant or advisory role: Celgene, Janssen, Sbbvie, AstraZeneca

Research funding: Janssen, Roche/Genetech, NanoString Technologies

A. Gerrie

Consultant or advisory role: Janssen, Abbvie, AstraZeneca, Sandoz

Honoraria: Janssen, Abbvie

Research funding: Abbvie, Roche Canada, Janssen, AstraZeneca

Educational grants: Janssen

T. Pickles

Honoraria: Abbvie, TerSera

Research funding: Astellas Oncology

L. Sehn

Consultant or advisory role: Celgene, Abbvie, Seattle Genetics, TG

Therapeutics, Janssen, Amgen, Roche, Gilead Sciences, Lundbeck,

apobiologix, Kite Pharma, Merck, Takeda, AstraZeneca, Acerta

Pharma, Sandoz‐Novartis, MorphoSys, Genmab, Verastem

Honoraria: Amgen, Apobiologix, Abbvie, Celgene, Gilead Sciences,

Janssen, Kite Pharma, Lundbeck, Merck, Roche, Seattle Genetics,

Takeda, Teva, TG Therapeutics, Karyopharm, AstraZeneca, Acerta

Pharma, Morphosys, Incyte, Debiopharm, Sandoz‐Novartis, Vera-

stem, Genmab

Research funding: Roche/Genetech, Teva

C. Freeman

Honoraria: BMSi, Seattle Genetics, Janssen, Amgen, Celgene, Sanoﬁ,

Abbvie

Educational grants: Roche, Teva

201 | PROGNOSTIC FACTORS IN ELDERLY PATIENTS WITH

CLASSICAL HODGKIN LYMPHOMA ‐ A JOINT ANALYSIS OF TWO

CLINICAL DATABASES

M. Fehr*

, N. Lang*

, L. Rubio

, S. Güsewell

, A. J. Templeton

S. Aeppli

, R. Tsang

, D. Hodgson

, A. Moccia

, M. Bargetzi

C. Caspar

, D. M. A. Brülisauer

, M. Ebnöther

, N. Fischer

A. Prica

, V. Kukreti

, G. Ghilardi

, F. Krasniqi

, U. J. Mey

W. Mingrone

, U. Novak

, P. Richter

, R. Kridel

, D. Rodin

M. Rütti

, A. Schmidt

, F. Stenner

, M. Voegeli

, T. Zander

M. Crump

, F. Hitz*

, J. Kuruvilla*

Cantonal Hospital St. Gallen, Medical Oncology and Haematology,

St. Gallen, Switzerland,

Hôpitaux Universitaires Genève, Department of

Oncology, Genève, Switzerland,

Manchester Royal Inﬁrmary,

Haematology, Manchester, UK,

Cantonal Hospital St. Gallen, Clinical

Trials Unit, St. Gallen, Switzerland,

Claraspital Basel, Oncology and

Haematology, Basel, Switzerland,

Princess Margaret Cancer Centre,

Medical Oncology and Haematology, Toronto, Canada,

Oncology

Institute of Southern Switzerland, Department of Medical Oncology,

Bellinzona, Switzerland,

Cantonal Hospital Aarau, Haematology, Aarau,

Switzerland,

Cantonal Hospital Baden, Oncology und Haematology,

Baden, Switzerland,

University Hospital Bern, Medical Oncology, Bern,

Switzerland,

Cantonal Hospital Winterthur, Medical Oncology and

Haematology, Winterthur, Switzerland,

Oncology Institute of Southern

Switzerland, Haematology, Bellinzona, Switzerland,

University Hospital

282

SUPPLEMENT ABSTRACTS

Basel, Oncology, Basel, Switzerland,

Cantonal Hospital Grisons,

Oncology and Haematology, Chur, Switzerland,

Cantonal Hospital

Olten, Centre for Oncology, Olten, Switzerland,

Princess Margaret

Cancer Centre, Radiation Oncology, Toronto, Switzerland,

Hospital Wil,

Medicine, Wil, Switzerland,

Stadtspital Triemli, Medical Oncology und

Haematology, Zürich, Switzerland,

Cantonal Hospital Baselland,

Oncology and Haematology, Liestal, Switzerland,

Cantonal Hospital

Luzern, Medical Oncology, Luzern, Switzerland

Background: Prognostic factors for elderly patients ≥60 years of

age with classical Hodgkin Lymphoma (cHL) are not well estab-

lished. Previous studies have shown that patient‐related factors

such as comorbidities and performance status (ECOG‐PS), disease‐

speciﬁc factors (extranodal disease) and markers of host inﬂam-

mation (e.g. neutrophil‐lymphocyte ratio [NLR]) can be associated

with clinical outcomes in elderly patients with cHL. Therefore

the aim of this study was to evaluate the association of cause‐

speciﬁc survival (CSS) and overall survival (OS) with age, stage,

Charlson comorbidity index (CCI) and these additional patient‐ and

disease‐related factors in a large dataset of elderly patients

with cHL.

Method: Joint analysis of Princess Margaret and Swiss elderly cHL

databases of patients from 2000 to 2018. Main inclusion criteria

were age ≥60 years, diagnosis of cHL, treatment with chemotherapy

(CT) or combined modality therapy (CMT). Patients with nodular‐

lymphocyte predominate HL (NLPHL) and treated with radio-

therapy alone were excluded. Univariable and multivariable models

were applied.

Results: Overall, 309 patients from 1 Canadian (n = 72) and 15 Swiss

centers (n = 237) were included. Excluded were 10 patients with RT

alone and 11 with NLPHL. Median age was 70 years (range 60 – 91),

median CCI was 7 (4 – 16), 17.2% of patients had stage I, 30.1 %

stage II, 29.9% stage III and 28.5% stage IV cHL. Overall, 5‐years

OS was 62.4% [95%CI 56.8 – 68.5] and 5‐years CSS was 82.6%

[78.1 – 87.4]. 189 (61.2%) patients were treated with CT alone, 120

(38.8.%) patients with CMT; 240 (77.7%) patients received

anthracycline‐containing CT, 69 (22.3%) patients received non‐

anthracycline‐containing CT.

In univariable analysis, age, stage, CCI, NLR and ECOG‐PS showed

signiﬁcant associations with both endpoints, all p‐values < 0.01.

Results of the multivariable analysis are demonstrated in table1.

Conclusion: In this large, international cohort of patients aged ≥60

years with cHL age, CCI and ECOG‐PS are independent factors

associated with OS. Age and stage are independently associated with

cause‐speciﬁc survival while NLR and extranodal disease are not

independently associated with clinical outcomes.

*contributed equally

Keywords: Diagnostic and Prognostic Biomarkers, Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

202 | MTV, TLG AND SUV MAX AS PROMISING PARAMETERS

TO PREDICT EARLY RESPONSE IN PATIENTS WITH HL TREATED

WITH ABVD. A RETROSPECTIVE SUB‐ANALYSIS OF THE GATLA‐

LH‐05 TRIAL

J. Iorio

, M. Eleta

, V. Plates

, L. Fiad

, M. Riddick

, A. Pavlovsky

IMAXE, Imagenes, CIUDAD DE BUENOS AIRES ‐ RECOLETA, Argentina

Introduction: Increased tumor burden is associated with inferior

outcomes in different lymphoma subtypes. Surrogates of tumor

burden, such as the maximum tumor dimension of the “bulkiest”

lesion on computed tomography (CT) have been used as a prognostic

index for many years. Recently, the total metabolic tumor volume

(MTV), tumor lesion glycolysis (TLG) and SUV max in basal PET‐CT

have emerged as promising and robust biomarkers of outcomes in

patients with Hodgkin's Lymphoma (HL). Interim PET‐CT is also a

well‐established prognostic factor for PFS in HL. We aim to identify

quantitive parameters from basal PET‐CT to predict early response in

interim PET (iPET) as a surrogate of PFS.

Methods: We performed a retrospective analysis of the database of

562 patients with HL who were enrolled between November 2008

and March 2020 in the GATLA‐LH‐05 trial. We searched for patients

who underwent a basal PET‐CT at the same PET center; MTV was

computed using 41% maximum standardize uptake value method:

TLG and SUVmax were derived. After 3 cycles of ABVD all patients

underwent an iPET. In this published trial patients with a negative

iPET had a PFS of 90% vs 65% in patients with iPET positive. Mann

Whitney test was performed to analyze difference of MTV, TLG and

SUV max, between PET positive and PET negative cohorts.

TABLE 1 Multivariable cox models: Hazard ratios with 95% CI and p‐values from Wald tests

Overall survival Cause‐speciﬁc survival

HR (95% CI) p‐value HR (95% CI) p‐value

Age (3 groups, per decennium) 1.85 (1.41‐2.45) <0.001 1.90 (1.23‐2.92) 0.004

Stage (I, II, III, IV, per level) 1.26 (0.99‐1.59) 0.056 2.15 (1.41‐3.28) <0.001

Charlson comorbidity index (3 groups: 4‐6, 7‐8, 9+, per level) 1.53 (1.18‐1.99) 0.001 1.24 (0.82‐1.89) 0.314

NLR (log‐transformed) 1.06 (0.84‐1.34) 0.629 1.04 (0.74‐1.46) 0.825

ECOG – Performance Status (3 groups: 0, 1, 2‐4, per level) 1.39 (1.07‐1.82) 0.015 1.26 (0.82‐1.93) 0.294

Extranodal involvement (yes vs. no) 1.15 (0.73‐1.79) 0.548 0.59 (0.30‐1.19) 0.143

SUPPLEMENT ABSTRACTS

283

Results: Of the total population, 64 patients had complete informa-

tion for this analysis, 40 (62.5%) patients had iPET negative, and 24

(37.5 %) iPET positive.

According to positive vs negative interim PET we identiﬁed the

following difference in basal PET. (Table 1):

In this retrospective analysis, difference between the distribution of

the baseline values of MTV and TLG variables, was statistically sig-

niﬁcant between the group of patients that achieved an IPET negative

vs those who had IPET positive (p = 0.001 and p = 0.005 respectively).

Finally, SUV max at baseline PET did not show signiﬁcant differences

between patients who did or did not achieve an iPET negative (p = 0.1).

Conclusions: In this explorative study, a high total MTV and TLG at

baseline PET are robust parameters to predict early response in the

interim PET. In this analysis we demonstrate the association of high

basal MTV and TLG as a predictor of early metabolic response, a

surrogate of PFS. This contributes to the growing evidence of the

importance of these values to predict outcome.

SUV max did not show correlation with early metabolic response.

A prospective clinical trial to reevaluate these important ﬁndings in a

larger group of patients, with an attempt to determine a reliable cut‐

off value in MTV and TLG is being planned.

Keywords: Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

203 | BASELINE MAXIMUM TUMOUR DIAMETER IS

ASSOCIATED WITH EVENT‐FREE SURVIVAL FOR PET‐NEGATIVE

PATIENTS WITH LIMITED‐STAGE HODGKIN LYMPHOMA:

ANALYSIS OF THE H10 AND RAPID TRIALS

E. H. Phillips

, N. Counsell

, T. Illidge

, M. Andre

, I. Aurer

, V.

Fiaccadori

, C. Fortpied

, A. Neven

, M. Federico

, L. Clifton‐Hadley

S. Barrington

, J. Raemaekers

, J. Radford

University of Manchester, The Christie NHS Foundation Trust and NIHR

Manchester Biomedical Research Centre, Manchester, UK,

University

College London, Cancer Research UK and UCL Cancer Trials Centre, London,

UK,

CHU UCL Namur, Department of Haematology, Yvoir, Belgium,

University Hospital Centre Zagreb, Division of Hematology, Department of

Internal Medicine, Zagreb, Croatia,

University College London, Cancer

Institute, London, UK,

European Organisation for Research and Treatment

of Cancer, EORTC Headquarters, Brussels, Belgium,

University of Modena

and Reggio Emilia, CHIMOMO Department, Modena, Italy,

King's College

London and King's Health Partners, King's College London and Guy's and St

Thomas' PET Centre, School of Biomedical Engineering and Imaging

Sciences, London, UK,

Radboud University Medical Center, Department of

Haematology, Nijmegen, Netherlands

Introduction: Trials evaluating response‐adapted use of radiotherapy

(RT) in limited‐stage Hodgkin lymphoma (LS‐HL) have shown that the

negative predictive value of PET is suboptimal. Additional biomarkers

are needed to facilitate a risk‐adapted approach. In the UK NCRI

RAPID trial, baseline maximum tumour diameter (MTD) was

associated with event‐free survival (EFS) for LS‐HL patients (pts)

who achieved complete metabolic response (CMR; Illidge et al,

Blood Advances 2020). The aim of this analysis was to validate these

ﬁndings in an independent cohort from the EORTC/LYSA/FIL H10 trial.

Methods: H10 recruited pts with stage I/II HL. Pts with CMR after 2x

ABVD received either chemotherapy alone (C) with 4‐6x ABVD (N =

540), or combined modality therapy (C + RT) with 3‐4x ABVD plus

RT (N = 1024). RAPID recruited pts with stage I/II HL, without

mediastinal bulk or B symptoms. Pts with CMR after 3x ABVD were

randomised to no further therapy (C; N = 211) or RT (C + RT; N =

208). Baseline MTD (in cm) was assessed by CT and locally reported.

We describe the association with EFS, deﬁned as progression or HL‐

related death, for pts with CMR, adjusted for treatment group and

stratiﬁed by trial (in pooled analyses).

Results: For H10 pts that were RAPID‐eligible (no B symptoms or

mediastinal bulk), we found a clear association between MTD and

EFS (N = 859; HR = 1.22, 95% CI: 1.07‐1.38, p < 0.01), similar to that

observed in RAPID (HR = 1.19, 95% CI: 1.02‐1.39, p = 0.02). Results

were consistent when adjusted for number of ABVD cycles and

EORTC risk stratiﬁcation. There was no evidence of an association

between MTD and EFS for RAPID‐ineligible H10 pts (N = 672; HR =

1.03, 95% CI: 0.96‐1.11, p = 0.37).

For RAPID‐eligible pts receiving C, there was a similar associa-

tion between MTD and EFS in both RAPID (HR = 1.20, 95% CI: 0.99‐

1.44, p = 0.06) and H10 (N = 303; HR = 1.19, 95% CI: 1.01‐1.40, p =

0.03). In a pooled analysis, the risk of relapse was on a continuum

with increasing MTD (N = 514; HR = 1.19, 95% CI: 1.01‐1.35, p <

TABLE 1 Baseline values of MTV, TLG and SUV max

Basal MTV Median Mean Standard deviation

PET + 167.27 ml. 263.49 ml. 339.86 ml.

PET ‐ 67.14 ml. 116.93 ml. 150.87 ml.

Basal TLG

PET + 584.98 ml. 890.44 ml. 898.90ml.

PET ‐ 225.53 ml. 453.78 ml. 785.61 ml.

Basal SUV

PET + 12.37 ml. 13.42 ml. 6.08 ml.

PET ‐ 10.77 ml. 11.01 ml. 6.54 ml.

284

SUPPLEMENT ABSTRACTS

0.01), with no clear MTD threshold above which we could identify a

marked difference in EFS. An MTD threshold of 5cm (AUC = 60.0%)

performed marginally better than 4cm, 3cm and 6cm (AUC = 59.2%,

58.5% and 56.7%, respectively) in time‐dependent receiver operating

characteristic curve analyses.

In an exploratory, pooled analysis of RAPID‐eligible pts treated

with C+RT, MTD was associated with EFS (N = 764; HR = 1.24, 95%

CI: 1.05‐1.46, p < 0.01). With only 20 events in this group, it was not

possible to evaluate MTD thresholds, and EFS rates were high irre-

spective of MTD (Figure).

Conclusions: This validation study conﬁrms the association between

baseline MTD and relapse risk for LS‐HL pts without B symptoms or

mediastinal bulk who achieve CMR, in an independent cohort. Out-

comes for pts with high MTD treated with C alone were suboptimal.

These ﬁndings inform discussion of risk for personalised application

of RT in LS‐HL and the design of future trials.

Keywords: Imaging and Early Detection – Other, Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

204 | SARCOPENIAIS AN INDEPENDENT PROGNOSTIC FACTOR

IN ELDERLY MALE PATIENTS WITH CLASSICAL HODGKIN

LYMPHOMA: RESULTS FROM A MULTICENTER EXPERIENCE

V. R. Zilioli

, D. Albano

, A. Arcari

, F. Merli

, A. Coppola

, G. Besutti

L. Marcheselli

, D. Gramegna

, C. Muzi

, M. Manicone

, M. Camalori

P. Ciammella

, G. Colloca

, A. Tucci

ASST Grande Ospedale Metropolitano Niguarda, Hematology, Milan, Italy,

ASST Spedali Civili, Nuclear Medicine, Brescia, Italy,

Ospedale Guglielmo

da Saliceto, Hematology, Piacenza, Italy,

Azienda USL ‐ IRCCS di Reggio

Emilia, Hematology, Reggio Emilia, Italy,

ASST Grande Ospedale

Metropolitano Niguarda, Radiology, Milan, Italy,

University of Modena and

Figure:

EFS according to treatment group and MTD for patients achieving in A) RAPID and B) H10

SUPPLEMENT ABSTRACTS

285

Reggio Emilia, Clinical and Experimental PhD program, Modena, Italy,

Fondazione Italiana Linfomi Onlus, Trial Ofﬁce Modena, Modena, Italy,

ASST Spedali Civili, Hematology, Brescia, Italy,

Azienda USL ‐ IRCCS di

Reggio Emilia, Radiotherapy, Reggio Emilia, Italy,

Fondazione Policlinico

Universitario A. Gemelli, IRCCS, Geriatrics, Rome, Italy

Introduction: Classical Hodgkin Lymphoma in the elderly (ecHL) is a

rare disease with dismal prognosis and no standard treatment. In

elderly lymphoma patients (pts) functional status evaluation helps

deﬁne different prognostic subgroups and may be useful to design

appropriate treatments. Sarcopenia has been associated with worse

survival in various solid tumors, but its impact in ecHL is unknown.

The aim of this retrospective multicenter study was to investigate the

prognostic role of sarcopenia in ecHL.

Methods: We retrospectively analyzed ≥65 years old ecHL pts

treated at 4 participating centers, who performed a baseline

comprehensive geriatric assessment (CGA) and high‐dose computed

tomography (CT) or positron emission tomography/CT (PET/CT)

before any treatment. Sarcopenia was measured as skeletal muscle

index (SMI, cm

) by the analysis of high dose CT or low‐dose PET/

CT images at the L3 level. The speciﬁc cut‐offs for the SMI were

determined by receiver operator curve (ROC) analysis and compared

with those studied in Diffuse Large B Cell Lymphoma (DLBCL) pts

(Lanic et al, Leuk Lymphoma 2014; Nakamura et al, Ann Hematol

2015). Survival functions (Progression Free Survival, PFS; Overall

Survival, OS) were calculated for the whole population and for

different subgroups deﬁned as per different sarcopenia cut‐off levels.

Results: One hundred and ﬁfty‐four pts (median age 71y, 76 females)

were included in the study. The median L3‐SMI was 42 cm2/m2. The

speciﬁc cut‐off derived in our male population was 45 cm2/m2; using

this cut‐off, 27 male pts (35%) were deﬁned as sarcopenic. After a

median follow‐up of 5.9 years, the overall 5‐year PFS and OS rates

were 53% and 65%, respectively, and were signiﬁcantly shorter in

sarcopenic males compared to non‐sarcopenic (PFS 31% vs 61%, p =

0.008; OS 51% vs 74%, p = 0.042) [Figure 1]. Applying DLBCL‐derived

sarcopenic thresholds, there were no signiﬁcant differences between

sarcopenic and non‐sarcopenic pts for both PFS and OS, with a sole

exception of a signiﬁcant reduced PFS in sarcopenic male pts using

Namakura‐cut off. The CGA‐determined frail functional status was an

independent adverse prognostic factor for both female and male pts.

Conclusions: Baseline evaluation of sarcopenia through radiological

examinations performed for ecHL staging may help deﬁne a pro-

portion of male pts with unfavorable outcome with current treatment

strategies. Also the functional status evaluation could allow to

identify a frail subgroup of pts with worse outcome. Prospective

studies are warranted to better deﬁne the effective role and utility of

this approach in the setting of ecHL.

Keywords: Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

205 | GUT MICROBIOTA ROLE IN RESPONSE TO CHECKPOINT

INHIBITOR TREATMENT IN PATIENTS WITH RELAPSED/

REFRACTORY B‐CELL HODGKIN LYMPHOMA: AN INTERIM

ANALYSIS FROM MICRO‐LINF STUDY

B. Casadei

, S. Guadagnuolo

, M. Barone

, S. Turroni

, L. Argnani

P. Brigidi

, P. L. Zinzani

IRCCS Azienda Ospedaliero‐Universitaria di Bologna Istituto di Emato-

logia “Seràgnoli”, and Dipartimento di Medicina Specialistica, Diagnostica

e Sperimentale Università di Bologna, n/a, Bologna, Italy,

University of

FIGURE 1 OS and PFS according to sarcopenic status deﬁned by our speciﬁc population cut‐off [<45 cm

] in male patients

286

SUPPLEMENT ABSTRACTS

287

Bologna, Department of Medical and Surgical Sciences, Bologna, Italy,

University of Bologna, Department of Pharmacy and Biotechnology,

Bologna, Italy

Background: Single‐agent monoclonal antibodies targeting the im-

mune checkpoint PD‐1 (programmed death 1) are an efﬁcient and

safe therapeutic option in patients with relapsed/refractory B‐cell

lymphoma. However, many patients progress or lose response to

anti‐PD1. Recent studies have highlighted the role of the gut

microbiota (GM) in inﬂuencing the response to chemo‐

immunotherapeutic agents. Here we hypothesize that the GM dy-

namics in B‐cell lymphoma patients during anti‐PD1 therapy corre-

late with treatment response.

Methods: From December 2017 to December 2020 we enrolled 17

patients (12 with classical Hodgkin lymphoma [cHL] and 5 with pri-

mary mediastinal B‐cell lymphoma) treated with anti‐PD1 due to

relapsed/refractory disease. Feces were collected at baseline, before

each therapy cycle, at response assessment (during both therapeutic

course and follow‐up) and for grade ≥2 adverse events, and proﬁled

through Illumina sequencing. At each time point, patients compiled a

7‐day weighted food intake record that was analyzed by MètaDieta

(METEDA).

Results: We report the results of the ﬁrst 6 patients enrolled, all

affected by cHL. Median age was 31 years (range 26‐71), 5 patients

were female. Five patients were refractory to the last therapy, with a

median of previous treatments of 3 (range 3‐5). All patients dis-

continued treatment: 3 due to disease progression; 2 achieved

complete remission and interrupted to consolidate with autologous

stem cell transplantation; the last due to grade 3 adverse event

despite partial remission. The median number of anti‐PD1 cycles was

15 (range 7‐18).

The baseline GM separated from that of age/gender‐matched

healthy controls, being enriched in the pathobiont Collinsella while

depleted of health‐associated taxa, e.g. Faecalibacterium, Rumino-

coccus, Coprococcus and Roseburia (p < 0.05; Figure 1A). The GM

dynamics along anti‐PD1 treatment were distinct in relation to the

therapeutic response, with greater temporal variability of alpha di-

versity in responders (Figure 1B). The latter consumed more fat and

fewer carbohydrates.

Conclusions: The GM of patients with relapsed/refractory B‐cell

Hodgkin lymphoma is dysbiotic and shows distinct trajectories

during anti‐PD1 treatment, closely related to the therapeutic

response.

Keywords: Diagnostic and Prognostic Biomarkers, Immunotherapy

No conﬂicts of interest pertinent to the abstract.

206 | CHARACTERIZATION OF CANCER ASSOCIATED

FIBROBLASTS IN CLASSICAL HODGKIN LYMPHOMA

K. Karihtala

, S.‐K. Leivonen

, M.‐L. Karjalainen‐Lindsberg

A. Östman

, T. Pellinen

, S. Leppä

University of Helsinki, Faculty of Medicine, Research Program Unit,

Applied Tumor Genomics, Helsinki, Finland,

Helsinki University Hospital,

Department of Pathology, Helsinki, Finland,

Karolinska Institutet,

Department of Oncology‐Pathology, Stockholm, Sweden,

Institute for

Molecular Medicine Finland, (FIMM), Helsinki, Finland

Introduction: Cancer‐associated ﬁbroblasts (CAFs) are a heteroge-

neous cell population with diverse functions. They constitute an

important stromal component of the tumor microenvironment (TME),

are in close crosstalk with tumor cells, regulate immune responses and

promote tumor progression. In classical Hodgkin lymphoma (cHL), the

role of CAFs is largely undeﬁned. Here, we aimed to characterize

distinct CAF subsets from diagnostic cHL samples and associate the

ﬁndings with other TME cells, immune response genes, clinical char-

acteristics and outcome of patients with previously untreated cHL.

Methods: CAFs as well as tumor associated macrophages, T cells and

different checkpoint molecules were phenotyped from diagnostic

131 cHL samples using multiplex immunohistochemistry (mIHC) with

digital image analysis. Platelet‐derived growth factor receptor

(PDGFR) α and β, ﬁbroblast‐activation protein (FAP) and α‐smooth

muscle actin (α‐SMA) were utilized as markers for CAFs. Nanostring‐

based data from a 770‐gene immune panel was used to correlate

CAF proportions with gene expression.

Results: Median age of the patients was 30 years (range 16‐83), 78%

had nodular sclerosis subtype and 56% advanced stage. Primary

treatment (85%) was mostly doxorubicin, bleomycin, vinblastine,

dacarbazine (ABVD), and in limited stage disease, ABVD in combi-

nation with radiotherapy. At the median follow‐up time of 55 months

(range 7‐229), 22% of the patients relapsed and 8% died. Five‐year

freedom from treatment failure (FFTF) was 79% and overall sur-

vival (OS) 91%.

From all cells in the cHL TME, 20% were PDGFRβ (range 0.2‐

92%), 19% FAP (range 0‐88%), 16% α‐SMA (range 2‐56%), and 1%

PDGFRα (range 0.1‐58%) positive. In Cox univariate analysis, high

proportion of FAP

cells associated with inferior FFTF (HR 1.25, 95%

CI 1.0‐1.5, P = 0.020), also after adjustment by age.

In a small cHL subgroup, FAP

and PDGFRα

markers were co‐

localized. Interestingly, PDGFRα

FAP

double positive phenotype

translated to better FFTF and OS (5‐y FFTF 100 % vs. 76%, P = 0.035;

5‐y OS 100% vs. 90%, P = 0.270). Patient demographics were equally

distributed between the subgroups. According to the pathway analysis,

focal adhesion and extracellular matrix genes were enriched in the

cHLs displaying PDGFRα

FAP

phenotype. PDGFRα

FAP

pheno-

type associated positively with high proportion of tumor associated

macrophages (P = 0.026), and negatively with T cells (P = 0.006) and

checkpoint molecule indoleamine 2,3 dioxygenase 1 (IDO‐1)

cells (P =

0.002). In addition, IDO1 mRNA levels correlated inversely with the

proportion of PDGFRα

FAP

cells (ρ = −0.530, P < 0.001).

Conclusions: Our data demonstrate that CAF subsets are clinically

relevant in cHL, and suggest that a newly identiﬁed subset of

PDGFRα

FAP

CAFs has prognostic impact on survival in cHL patients.

The research was funded by: grants from the Academy of Finland (S.

L.), Finnish Cancer Organizations (S.L.), Sigrid Juselius Foundation (S.

288

SUPPLEMENT ABSTRACTS

L.), University of Helsinki (S.L.), Helsinki University Hospital (S.L.),

University of Helsinki, Doctoral Programme in Clinical Research (K.

K.), Finnish Society for Oncology (K.K.) and Orion Research Foun-

dation (K.K.)

Keywords: Tumor Biology and Heterogeneity, Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

K. Karihtala

Educational grants: Gilead

S. Leppä

Consultant or advisory role: Janssen‐Cilag, Novartis, Roche, Takeda,

Merck

Honoraria: Roche, Takeda, Merck, Celgene

Research funding: Janssen‐Cilag, Roche, Takeda, Bayer, Celgene

207 | TRACKING CLONAL HEMATOPOIESIS IN PATIENTS

WITH CLASSICAL HODGKIN'S LYMPHOMA

*A. Marra (co‐ﬁrst author)

, *A. Venanzi (co‐ﬁrst author)

, *G.

Schiavoni (co‐ﬁrst author)

, S. G. Milner

, R. Limongello

, A. Santi

, V.

Pettirossi

, S. Ultimo

, L. Tasselli

, A. Pucciarini

, L. Falini

, S.

Sciabolacci

, M. P. Martelli

, P. Sportoletti

, S. Ascani

, ^B. Falini (co‐

last author)

, ^E. Tiacci (co‐last author)

Institute of Hematology and Center for Hemato‐Oncology Research,

University and Hospital of Perugia ‐ Italy, Medicine, Perugia, Italy

Introduction: Clonal hematopoiesis (CH) is frequent in the elderly

and predisposes to hematological malignancies, mostly of myeloid

and T‐cell origin. CH incidence and tissue trajectories are not well

characterized in classical Hodgkin lymphoma (cHL), a B‐cell neoplasm

frequent in the young and uniquely featuring a small tumor clone of

FIGURE 1

SUPPLEMENT ABSTRACTS

289

Hodgkin/Reed‐Sternberg (HRS) cells interspersed in a tumor‐

supportive microenvironment largely inﬁltrated by hematopoietic

cells.

Methods: 40 cHL cases were studied for CH, by whole‐exome and/or

targeted sequencing (mean unique coverage ∼150X and ∼1000X,

respectively) of microdissected tumor cells, and matched non‐

neoplastic blood cells (n = 27 cases) and/or lymphoid cells micro-

dissected from the tissue biopsy (n = 14 cases).

Results: 5/40 cases (12.5%) had blood and/or tissue CH, including 3/5

with >70 years and 2/35 < 70 years (Fig. 1A). In 3/5 CH cases (aged

30, 45 and 73 years), CH extensively spread through the non‐

neoplastic tissue microenvironment (32%, 92%, and 60% of cells),

being respectively driven by DNMT3A

R882H

(Case 1), mutant

KRAS

G60D

(Case 2) and DNMT3A

R882H

+ TET2

Q1274*

(Case 5).

Notably, in Case 5 (73 years old), CH originated also the tumor cell

clone, which was infected by the Epstein‐Barr virus and had almost

no other somatic mutations exome‐wide; this is the ﬁrst description,

in a cHL tumor cell clone, of mutant DNMT3A

R882

, a hotspot in

myeloid and T‐cell neoplasms.

In Case 1 (45 years old), the same mutation determined a massive

blood CH (DNMT3A

R882H

in 94% leukocytes and in 96% B cells) that

was surprisingly absent from the tumor cell clone (instead carrying

STAT6 and SOCS1 mutations, typical of cHL) and led, 6 years after

therapy for cHL, to a likely therapy‐unrelated NPM1‐mutated acute

myeloid leukemia (with normal karyotype, wild‐type TP53 and

PPM1D) (Fig. 1B). Thus, CH trajectories must be carefully disen-

tangled to correctly interpret the histogenesis and pathogenesis of

multiple blood cancers arising in patients with CH.

Interestingly, all 3 cases with extensive CH propagation in cHL tissue

microenvironment, showed a polyclonal status of T‐cell receptor

gene rearrangement, thus proving that CH‐associated mutations

occurred in a bone marrow stem/progenitor cell before T‐cell lineage

commitment.

Finally, all these 3 cases progressed after ﬁrst‐line chemotherapy,

versus 11/35 (31%; p‐value 0.043) evaluable cases with absent or

non‐extensive tissue CH, who otherwise had similar clinical features

and received the same ﬁrst‐line therapy.

Conclusions: CH can be observed in the cHL tissue, can originate the

tumor clone and can propagate to large part of its microenvironment.

Considering that both HRS cells and the microenvironment sup-

porting its growth play key roles in cHL pathogenesis, CH might

contribute to the development of this B‐cell lymphoma and inﬂuence

its prognosis.

EA – previously submitted to AACR and EHA 2021.

The research was funded by: This research was funded by a grant on

cHL to ET from AIRC (IG 2019‐ ID. 23732 project – P.I. Tiacci Enrico); a

grant on AML to BF from AIRC (IG 2019 n. 23604); a grant on AML to

BF from ERC (Advanced Grant 2016 n. 740230), the Leopold Griffuel

prize from ARC to BF; and a grant on cHL to GS from the Department of

Medicine ‐ University of Perugia (Ricerca di Base 2017‐2019).

Keywords: Tumor Biology and Heterogeneity, Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

PEDIATRIC LYMPHOMAS

208 | A UK POPULATION‐BASED STUDY OF NON‐HODGKIN

LYMPHOMA IN TEENAGERS AND YOUNG ADULTS (TYA)

DELAYED DIAGNOSIS AND DEATH

R. Carr

, K. Stevens

, G. Anyaegbu

, J. Fidalgo

Guy's & St Thomas' Hospital, Haematology, London, UK,

University

Hospital Southampton, Haematology, Southampton, UK,

Addenbrookes

Hospital, Haematology, Cambridge, UK

Introduction: Non‐Hodgkin Lymphoma may present with non‐

speciﬁc symptoms or lymphadenopathy, most commonly due to

infection. Late diagnosis of cancers in TYA patients is well recognised

and surveys of TYAs with cancer ﬁnd many have repeated visits to

primary care physicians (GPs) before diagnosis. As part of a national

study of NHL in young adults information was recorded on the

pathway to diagnosis to understand the frequency and consequence

of diagnosis delay.

Methods: During 2015‐2018 29 hospitals recruited newly diagnosed

patients aged 15–29y into an observational study of NHL diagnosis,

stage, treatment and survival. Information was requested on date of

ﬁrst consultation with a medical professional, route to hospital

admission, ie. GP referral or self presentation to an emergency

department, and descriptions of repeated visits. Delay was recorded

if there was >62 days between ﬁrst consultation and diagnosis, a

clear history of relevant symptoms or signs before seeking medical

advice, or evidence of missed opportunities by GP or hospital to di-

agnose a malignancy. In addition, the study received English Cancer

Registry data on 624 15‐29y old diagnosed over 3y 2015‐2017,

recording diagnosis and deaths.

Results: Nine study hospitals contributed to this sub‐study; 171/191

patients had their diagnostic pathway recorded. Sixty (35%) had ev-

idence of delayed diagnosis recorded; by age group 15‐19y 21/45

(47%), 20‐24y 23/70 (33%), age 24‐29y 16/56 (29%). The most

frequent cause was patient delay in seeking advice (47%), delayed

referral by GP (28%), or hospital failure (25%), eg. diagnosing a pelvic

mass as ovarian cyst in 2 patients. Delay was not inﬂuenced by

gender: 34 male, 36 female. Advanced disease (stage 4) was more

common in delay patients 34/60 (57%), compared to 47% of similar

patients in the full cohort. Deaths, 10/60 (17%) in ‘delayed’ patients

compared to 16% in all recruited patients.

Cancer Registry data highlights the consequence of missed diagnosis.

Diagnosis and death date was the same for 6 individuals aged 20‐

29y; 2 conﬁrmed as died at home, 1 immediately following hospital

admission, 3 without additional information. Another (23y) with T‐

lymphoblastic NHL died of cardiac tamponade 3 days after visting

an emergency department, but discharged.

Conclusions: The qualitative evidence from this sub‐study demon-

strates frequent failure to recognise malignancy in this age group, but

equally reluctance of patients to seek early medical advice for un-

usual symptoms and signs. The observation that mortality was similar

in frequency in the ‘delay’ subgroup compared to all patients on the

290

SUPPLEMENT ABSTRACTS

one hand suggests delayed diagnosis may not compromise outcome,

but equally may indicate that delay in seeking medical advice is to

some extent common to all. Achieving better outcomes needs raised

awareness by both young people and health professionals, as well as

expert treatment.

The research was funded by: Gilead UK and Ireland Fellowship

ProgrammeLeukaemia UK

Keywords: Non‐Hodgkin (Pediatric, Adolescent, and Young Adult)

No conﬂicts of interest pertinent to the abstract.

PERIPHERAL T/NK CELL LYMPHOMAS

209 | A PHASE 2B OPEN‐LABEL SINGLE ARM STUDY TO

EVALUATE THE EFFICACY AND SAFETY OF HBI‐8000

(TUCIDINOSTAT) IN PATIENTS WITH RELAPSED OR

REFRACTORY PERIPHERAL T‐CELL LYMPHOMA (PTCL)

W. S. Kim

, S. Rai

, K. Ando

, I. Choi

, K. Izutsu

, N. Tsukamoto

M. Yokoyama

, K. Tsukasaki

, J. Kuroda

, J. Ando

, M. Hidaka

Y. Koh

, H. Shibayama

, T. Uchida

, D. H. Yang

, K. Ishitsuka

K. Ishizawa

, J. S. Kim

, H. G. Lee

, H. Minami

, H. S. Eom

H. Nagai

, M. Kurosawa

, J. H. Lee

, W. S. Lee

, T. Shindo

D. H. Yoon

, S. Yoshida

, M. Gillings

, H. Onogi

, K. Tobinai

Samsung Medical Center, Division of Hematology‐Oncology, Seoul, Ko-

rea,

Kindai University Hospital, Department of Hematology and Rheu-

matology, Faculty of Medicine, Osakasayama, Japan,

Tokai University

Hospital, Department of Hematology and Oncology, Isehara, Japan,

National Hospital Organization Kyushu Cancer Center, Department of

Hematology, Fukuoka, Japan,

National Cancer Center Hospital, Depart-

ment of Hematology, Tokyo, Japan,

Gunma University Hospital,

Oncology Center, Maebashi, Japan,

The Cancer Institute Hospital of

Japanese Foundation for Cancer Research, Department of Hematology

and Oncology, Tokyo, Japan,

International Medical Center, Saitama

Medical University, Department of Hematology, Saitama, Japan,

Kyoto

Prefectural University of Medicine, Division of Hematology and Oncology,

Kyoto, Japan,

Juntendo University Hospital, Department of Hematology,

Tokyo, Japan,

National Hospital Organization Kumamoto Medical

Center, Department of Hematology, Kumamoto, Japan,

Seoul National

University Hospital, Department of Internal Medicine, Seoul, Korea,

Osaka University Hospital, Department of Hematology and Oncology,

Suita, Japan,

Japanese Red Cross Nagoya Daini Hospital, Department of

Hematology and Oncology, Nagoya, Japan,

Chonnam National Univer-

sity Hwasun Hospital, Department of Hematology, Hwasun, Korea,

Kagoshima University Hospital, Department of Hematology and Rheu-

matology, Kagoshima, Japan,

Yamagata University Hospital, Depart-

ment of Third Internal Medicine, Yamagata, Japan,

Yonsei University

College of Medicine, Severance Hospital, Division of Hematology,

Department of Internal Medicine, Seoul, Korea,

Konkuk University

Medical Center, Department of Hematology & Oncology, Seoul, Korea,

Kobe University Graduate School of Medicine and Hospital, Department

of Medical Oncology/Hematology, Kobe, Japan,

National Cancer Center,

Center for Hematologic Malignancy, Goyang‐si, Korea,

National Hos-

pital Organization Nagoya Medical Center, Clinical Research Center,

Nagoya, Japan,

National Hospital Organization Hokkaido Cancer Cen-

ter, Department of Hematology, Sapporo, Japan,

Gachon University Gil

Medical Center, Division of Hematology, Incheon, Korea,

Inje University

Busan Paik Hospital, Department of Internal Medicine, Busan, Korea,

Kyoto University Hospital , Department of Hematology and Oncology,

Kyoto, Japan,

Asan Medical Center, University of Ulsan College of

Medicine , Department of Oncology, Seoul, Korea,

National Hospital

Organization Nagasaki Medical Center, Department of Hematology,

Omura, Japan,

HUYA Bioscience International LLC, CEO & Executive

Chair, CA, USA,

HUYA Bioscience International, Executive Vice Presi-

dent, Head of Clinical Development‐Japan, Tokyo, Japan

Introduction: PTCL is a type of non‐Hodgkin lymphoma (NHL) and it

represents approximately 10‐20% of all NHL. Patients with relapsed

or refractory (R/R) PTCL have a poor prognosis. Although several

new agents for R/R PTCL have been developed, response rates are

generally modest and durations of response are relatively short.

Thus, there are still unmet needs for patients with R/R PTCL. HBI‐

8000 (tucidinostat) is a histone deacetylase inhibitor (HDACi) that

has been approved for treatment of PTCL in China.

Method: Patients after receiving ≥1 prior systemic therapy with a

histologically diagnosed as PTCL and at least 1 measurable lesion

received HBI‐8000 40 mg orally twice a week.

The primary endpoint was objective response rate (ORR) that was

evaluated by Independent Overall Efﬁcacy Review Committee ac-

cording to the revised criteria for response assessment in lymphoma

(Cheson et al, 2014). Other endpoints included progression‐free

survival (PFS), duration of response (DOR) and safety. ORR was

also evaluated by subtypes.

The target ORR was 30% and the target number of patients for ef-

ﬁcacy analysis was 40. AE severity was deﬁned according to Common

Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Our

study started in March 2017. We present the results of primary

analysis at the data cut‐off date of 18 March 2019, when the last

patient completed the Cycle 5 Day 1. (NCT02953652)

Results: A total of 55 patients (median age: 71 years, range 38‐87)

received at least 1 dose of HBI‐8000. Overall, 69% (38/55) had

received 2 or more prior therapies, including 15% (8/55) of subjects

had received 5 or more therapies, before entering the study. The

median time from last treatment to the start of the study drug was

97 days (range: 29, 3861). As of data cut‐off, 8 patients (15%) were

still on treatment. Median duration of exposure was 80 days (ranging

10‐580).

Among 46 patients in per protocol set, ORR was 46% (21/46 [95% CI:

31, 61]). ORR by subtype was 35% (12/34) in PTCL‐NOS; 88% (7/8)

in AITL; 33% (1/3) in ALCL, ALK‐; and 100% (1/1) in EATL. Median

PFS was 5.6 months and median DOR was 11.5 months. Median OS

was 22.8 months.

All 55 patients experienced adverse events. The incidence of

Grade ≥3 AEs was 84% and most AEs were laboratory abnor-

malities include thrombocytopenia (51%), neutropenia (36%) and

SUPPLEMENT ABSTRACTS

291

lymphopenia (22%). Serious AEs related to study drug were re-

ported in 18% (10/55). AEs led to study drug interruption or dose

reduction in 73% (40/55) and led to the discontinuation of study

drug in 33% (18/55), respectively.

Conclusions: Our results showed that tucidinostat has an efﬁcacy

with acceptable safety proﬁle in patients with R/R PTCL regardless of

its histopathological subtypes. This suggests that tucidinostat is a

clinically meaningful treatment option for patients with R/R PTCL

where no standard treatment is established, and strong unmet

medical needs exist.

The research was funded by: HUYA Bioscience International

Keywords: Therapeutics and Clinical Trials in Lymphoma ‐ Other

Conﬂicts of interests pertinent to the abstract

W. S. Kim

Research funding: Roche, Sanoﬁ, Pﬁzer, J&J, Celltrion, Kyowa‐kirin,

Donga ST, Mundipharma

S. Rai

Honoraria: Chugai

K. Izutsu

Research funding: HUYA Bioscience International

M. Yokoyama

Consultant or advisory role: Chugai

Research funding: Kyowa‐kirin

K. Tsukasaki

Consultant or advisory role: Daiich‐Sankyo, Ono, HUYA Bioscience

International, Yakult Honsha

Honoraria: Celgene, Chugai, Bayer, Eisai, Kyowa‐kirin, Mundipharma,

Takeda

Research funding: Daiich‐Sankyo, HUYA Bioscience International,

Celgene, Chugai, Bayer, Eisai

M. Hidaka

Honoraria: Janssen

Research funding: Chugai

Y. Koh

Employment or leadership position: GenomeOpinion

Stock ownership: GenomeOpinion

H. Shibayama

Consultant or advisory role: Chugai, Ono, Abbvie, and AstraZeneca

Honoraria: Takeda, Novartis, Celgene, Janssen, Chugai, Kyowa‐kirin,

Ono, Eisai, Nippon Shinyaku, Otsuka, Daiich‐Sankyo, BMS, Pﬁzer,

Sanoﬁ, and Fujimoto

Research funding: Janssen, Novartis, Chugai, Ono, Eisai, HUYA

Bioscience International, Abbvie, AstraZeneca, Sanoﬁ, Astellas, Teijin,

Shionogi, Taiho, Celgene, Takeda, MSD, Sumitomo Dainippon, Nippon

Shinyaku, and Daiich‐Sankyo

K. Ishizawa

Research funding: Novartis, AbbVie, Bayer, SymBio, Otsuka, Pﬁzer,

Takeda, Kyowa‐Kirin

Other remuneration: Takeda, Celgene, Ono, Novartis, Chugai, Eisai

H. Minami

Honoraria: Bayer, BMS, Celgene, Chugai, Daiich‐Sankyo, Sumitomo

Dainippon, Eisai, Janssen, Kyowa‐Kirin, Merck Serono, MSD, Ono,

Otsuka, Pﬁzer, Sanoﬁ, Takeda, Genomic Health, Abbvie, Taiho, Lilly,

Novartis

Research funding: Astellas, Bayer, Behringer, BMS, Chugai, Daiich‐

Sankyo, Sumitomo Dainippon, Eisai, Kyowa‐Kirin, Merck Serono,

MSD, Nippon Shinyaku, Ono, Sanoﬁ, Takeda, CSL Behring, Nippon

Fig. The Best Percent Change from Baseline in Total Tumor Size of Target Lesion (PPS)

292

SUPPLEMENT ABSTRACTS

Kayaku, Shionogi, Taiho, Lilly, Mitsubishi Tanabe, AZ, Pﬁzer, Amgen,

Novartis

H. Nagai

Honoraria: Eisai, Chugai, Takeda, Celgene, Mundipharma

Research funding: AstraZeneca, Celgene, Mundipharma, Zenyaku

Kogyo, Takeda, Chugai, Bayer

S. Yoshida

Research funding: Kyowa‐Kirin

M. Gillings

Employment or leadership position: HUYA Bioscience International

Stock ownership: HUYA Bioscience International

H. Onogi

Employment or leadership position: HUYA Bioscience International

K. Tobinai

Consultant or advisory role: Celgene, Zenyaku Kogyo, HUYA

Bioscience International, Daiich‐Sankyo, Takeda, Mundipharma, Ono

Honoraria: Zenyaku Kogyo, Eisai, Takeda, Mundipharma, HUYA

Bioscience International, Kyowa‐Kirin, Celgene, Chugai, Ono, Yakult

Honsha, Daiich‐Sankyo, Solasia

210 | A PHASE 2B STUDY TO EVALUATE THE EFFICACY AND

SAFETY OF TUCIDINOSTAT (HBI‐8000) IN JAPANESE PATIENTS

WITH RELAPSED OR REFRACTORY ADULT T‐CELL LEUKEMIA‐

LYMPHOMA (ATL)

K. Izutsu

, A. Utsunomiya

, T. Jo

, S. Yoshida

, K. Ando

, I. Choi

Y. Imaizumi

, K. Kato

, M. Kurosawa

, S. Kusumoto

, T. Miyagi

, E.

Ohtsuka

, O. Sasaki

, H. Shibayama

, K. Shimoda

, Y.

Takamatsu

, K. Takano

, K. Tsukasaki

, S. Makita

, K. Yonekura

J. Taguchi

, M. Gillings

, H. Onogi

, K. Tobinai

National Cancer Center Hospital, Department of Hematology, Tokyo,

Japan,

Imamura General Hospital, Department of Hematology,

Kagoshima, Japan,

Japanese Red Cross Nagasaki Genbaku Hospital,

Department of Hematology, Nagasaki, Japan,

National Hospital

Organization Nagasaki Medical Center, Department of Hematology,

Omura, Japan,

Tokai University Hospital, Department of Hematology/

Oncology, Kanagawa, Japan,

National Hospital Organization Kyushu

Cancer Center, Department of Hematology, Fukuoka, Japan,

Nagasaki

University Hospital, Department of Hematology, Nagasaki, Japan,

Kyushu University Hospital, Department of Hematology, Oncology &

Cardiovascular medicine, Fukuoka, Japan,

National Hospital

Organization Hokkaido Cancer Center, Department of Hematology,

Sapporo, Japan,

Nagoya City University Hospital, Division of

Hematology and Oncology, Aichi, Japan,

Heartlife Hospital, Department

of Hematology, Okinawa, Japan,

Oita Prefectural Hospital, Department

of Hematology, Oita, Japan,

Miyagi Cancer Center, Division of

Hematology, Miyagi, Japan,

Osaka University Hospital, Department of

Hematology and Oncology, Osaka, Japan,

University of Miyazaki

Hospital, Department of Hematology, Miyazaki, Japan,

Fukuoka

University Hospital, Department of Medical Oncology, Hematology and

Infectious Diseases, Fukuoka, Japan,

Oita University, Department of

Medical Oncology and Hematology, Faculty of Medicine, Oita, Japan,

International Medical Center, Saitama Medical University, Department

of Hematology, Saitama, Japan,

Imamura General Hospital, Department

of Dermatology, Kagoshima, Japan,

HUYA Bioscience International LLC,

CEO & Executive Chair, San Diego, USA,

HUYA Bioscience International

LLC, Executive Vice President, Head of Clinical Development‐Japan,

Tokyo, Japan

Introduction: Tucidinostat (HBI‐8000) is a class I selective oral his-

tone deacetylase inhibitor with immunomodulatory effects including

enhanced cell‐mediated toxicity, with activation of enhanced tumor‐

speciﬁc cytotoxic T‐lymphocytes and suppression of regulatory T‐

lymphocytes.

In the phase 1 study in Japanese patients with relapsed or re-

fractory (R/R) non‐Hodgkin lymphoma including those with adult

T‐cell leukemia‐lymphoma (ATL), tucidinostat showed tolerability

and manageable safety proﬁle as well as efﬁcacy signals especially

in patients with ATL. This phase 2 study further evaluated the ef-

ﬁcacy and safety of tucidinostat in patients with R/R aggressive

ATL.

Method: Key inclusion criteria included; histopathological or cyto-

logical diagnosis of ATL of acute, lymphoma or unfavorable chronic

types; relapsed or refractory disease after receiving prior systemic

therapy including mogamulizumab or ≥1 prior systemic therapy with

cytotoxic chemotherapy in case of intolerance/contraindication for

mogamulizumab. Patients were to receive tucidinostat 40 mg twice a

week with a 28‐day cycle. Tucidinostat was continued until disease

progression or the development of unacceptable toxicity. The pri-

mary endpoint was objective response rate (ORR). Secondary end-

points included progression‐free survival (PFS), duration of response

(DOR) and safety. (NCT02955589)

Results: A total of 23 patients were treated with tucidinostat and

were included in both efﬁcacy and safety analysis sets. The median

age was 72 years (range: 60‐89), and 35% (8/23) were female. The

median number of prior chemotherapies was 2. All patients had prior

mogamulizumab treatment. As for ATL subtype, acute, lymphoma and

unfavorable chronic types constitute 57% (13/23), 35% (8/23), and

9% (2/23), respectively. The median time from last treatment to the

initiation of the study drug was 89 days (range: 30‐496).

Out of 23 patients, 7 showed objective responses including 1

complete response, and ORR was 30% [95% CI: 13, 53]. ORR by ATL

subtypes were 46% (6/13) in acute type, 13% (1/8) in lymphoma type,

and 0% (0/2) in unfavorable chronic type. Median PFS and median

DOR were 1.7 months and 6.5 months, respectively.

All 23 patients experienced adverse events (AEs). Overall, 78%

(18/23) of patients had AEs of Grade ≥3 severity. Most of AEs were

hematologic including thrombocytopenia and neutropenia, followed

by non‐hematological AEs including decreased appetite and malaise.

Conclusions: The results of the present study are demonstrating

efﬁcacy in patients with R/R aggresive ATL with prior treatment

SUPPLEMENT ABSTRACTS

293

history of mogamulizumab. Toxicities were mainly hematologic,

which were manageable with supportive care and dose modiﬁcations.

This phase 2b study demonstrated that tucidinostat had clinically

meaningful efﬁcacy and an acceptable safety proﬁle in R/R aggressive

ATL.

The research was funded by: HUYA Bioscience International

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma, Therapeutics

and Clinical Trials in Lymphoma ‐ Other

Conﬂicts of interests pertinent to the abstract

K. Izutsu

Research funding: HUYA Bioscience International

A. Utsunomiya

Consultant or advisory role: HUYA Bioscience International, JIMRO

Honoraria: Novartis Pharma, Kyowa Kirin, Daiichi Sankyo, Bristol‐

Myers Squibb, Celgene, Pﬁzer, Minophagen Pharmaceutical, Jans-

sen Pharmaceutical, Chugai Pharmaceutical

S. Yoshida

Research funding: Kyowa Kirin

Y. Imaizumi

Honoraria: Celgene, Kyowa Kirin, Eisai , Bristol‐Myers Squibb,

Sumitomo Dainippon Pharma, SymBio Pharmaceuticals

K. Kato

Consultant or advisory role: AbbVie, AstraZeneca, Celgene, Chugai

Pharmaceutical, Eisai, Janssen Pharmaceutical, Novartis Pharma,

Daiichi Sankyo, Ono Pharmaceutical

Honoraria: Takeda Pharmaceutical, MSD, Kyowa Kirin, Janssen

Pharmaceutical, Celgene, Ono Pharmaceutical, Mundipharma, Sumi-

tomo Dainippon Pharma, Bristol‐Myers Squibb

Research funding: Chugai Pharmaceutical, Takeda Pharmaceutical,

Kyowa Kirin, AbbVie, Eisai, Janssen Pharmaceutical, Celgene, Ono

Pharmaceutical, Novartis Pharma, Daiichi Sankyo

S. Kusumoto

Honoraria: Chugai Pharmaceutical

H. Shibayama

Consultant or advisory role: Chugai Pharmaceutical, Ono Pharma-

ceutical, AbbVie, AstraZeneca

Honoraria: Takeda, Novartis, Celgene, Janssen, Chugai, Kyowa Kirin,

Ono, Eisai, Nippon Shinyaku, Otsuka, Daiichi Sankyo, Bristol‐Myers

Squibb, Pﬁzer, Sanoﬁ, Fujimoto

Research funding: Janssen, Novartis, Chugai, Ono, Eisai, HUYA

Bioscience International, AbbVie, AstraZeneca, Sanoﬁ, Astellas, Tei-

jin, Shionogi, Taiho, Celgene, Takeda, MSD, Sumitomo Dainippon

Pharma, Nippon Shinyaku, Daiichi Sankyo

K. Shimoda

Consultant or advisory role: Novartis Pharma, Takeda Pharmaceu-

tical, Bristol‐Myers Squibb, Celgene

Research funding: Perseus Proteomics, Pharma Essentia Japan,

AbbVie, Astellas Pharma, MSD, Chugai Pharmaceutical, Kyowa Kirin,

Pﬁzer, Novartis Pharma, Otsuka Pharmaceutical, Asahi Kasei Medical

Y. Takamatsu

Research funding: Takeda Pharmaceutical, Ono Pharmaceutical,

Chugai Pharmaceutical, Kyowa Kirin, Taiho Pharmaceutical

K. Tsukasaki

Consultant or advisory role: Daiichi Sankyo, Ono Pharmaceutical,

HUYA Bioscience International, Yakult Pharmaceutical Industry

Honoraria: Celgene, Chugai Pharmaceutical, Bayer Yakuhin, Eisai,

Kyowa Kirin, Mundipharma, Takeda Pharmaceutical

Research funding: Daiichi Sankyo, HUYA Bioscience International,

Celgene, Chugai Pharmaceutical, Bayer Yakuhin, Eisai

S. Makita

Honoraria: Celgene/BMS, Daiichi Sankyo, Eisai, Novartis Pharma,

Takeda Pharmaceutical

K. Yonekura

Honoraria: AbbVie, Celgene, Daiichi Sankyo, Eisai, Eli Lilly Japan,

Janssen Pharmaceuticals, Kaken Pharmaceutical, Kyowa Kirin, Mar-

uho, Minophagen Pharmaceutical, Novartis Pharma, Sanoﬁ, Taiho

Pharmaceutical, Torii Pharmaceutical, UCB Japan

M. Gillings

Employment or leadership position: HUYA Bioscience International

Stock ownership: HUYA Bioscience International

H. Onogi

Employment or leadership position: HUYA Bioscience International

K. Tobinai

Consultant or advisory role: Celgene, Zenyaku Kogyo, HUYA

Bioscience International, Daiichi Sankyo, Takeda Pharmaceutical,

Mundipharma, Ono Pharmaceutical

Honoraria: Zenyaku Kogyo, Eisai, Takeda Pharmaceutical, Mundi-

pharma, HUYA Bioscience International, Kyowa Kirin, Celgene,

Chugai Pharmaceutical, Ono Pharmaceutical, Yakult Pharmaceutical

Industry, Daiichi Sankyo, Solasia Pharma

211 | A PHASE II TRIAL OF REDUCED DOSE BRENTUXIMAB

VEDOTIN FOR CUTANEOUS T‐CELL LYMPHOMAS

N. Khan

, S. Noor

, S. Geller

, M. S. Khodadoust

, M. Kheterpal

H. Hancock

, T. Davey

, S. Ryu

, L. Perez

, A. Lares

, N. Ganesan

S. Sohail

, A. Santarosa

, N. Galasso

, E. Kim

, P. Myskowski

Y. H. Kim

, S. Horwitz

, A. Moskowitz

Memorial Sloan Kettering Cancer Center, Medicine, Lymphoma Service,

New York, USA,

Memorial Sloan Kettering Cancer Center, Dermatology,

New York, New York, USA,

Tel Aviv Sourasky Medical Center,

Dermatology, Tel Aviv, Israel,

Stanford University School of Medicine,

Department of Medicine, Division of Oncology & Department of

294

SUPPLEMENT ABSTRACTS

Dermatology, Stanford, California, USA,

Duke University Medical Center,

Dermatology, Durham, North Carolina, USA

Introduction: Mycosis fungoides (MF) is the most common cutaneous

T cell lymphoma. Brentuximab vedotin (BV) is a highly effective

therapy for MF with an overall response rate (ORR) of 65% in the

phase III ALCANZA trial (Prince et al, Lancet 2017). However, 44/66

(67%) of patients on BV developed peripheral neuropathy (PN) (G2, n

= 21; G3, n = 6), limiting treatment duration (median, 12 cycles). We

hypothesized that lower dose BV would produce acceptable efﬁcacy

with reduced PN for the treatment of MF.

Methods: This is a multicenter phase II study. We treated BV‐naïve

patients with MF (n = 19) in a Simon two‐stage design with ex-

pected ORR 35% and desired ORR of 65%. Patients were treated

with BV at 0.9 mg/kg. If <11 responses were seen at the end of

the second stage, the Simon 2 stage design restarted with BV at

1.2 mg/kg.

Responses are graded every 4 cycles. Global response is graded

using the International Society for Cutaneous Lymphomas consensus

criteria (Olsen et al, JCO 2011). PN is graded using Common Ter-

minology Criteria for Adverse Events v. 4.0 (CTCAE) and the Total

Neuropathy Score Clinical (TNSc). Health Related Quality of Life

(HRQoL) is self‐reported by patients using the FACT‐Lym, FACT‐

GOG‐NTX and Skindex‐29 questionnaires.

Results: 19 patients were treated in Cohort 1 with BV at 0.9 mg/kg,

with ORR of 42% (8 partial responses (PR), 0 complete responses

(CR)) (Fig 1A). Median PFS was 21.9 months (95% CI, 4.8 – NR) and

median duration of response was 21.1 mon (95% CI, 5.9‐NR). Median

time to best response was 2.5 months (range, 2.1 – 7.8 mon), or 3

cycles (range, 3‐11 cycles) (Fig 1A). 8/19 (42%; 95% CI, 20‐66%)

patients developed PN. 5/8 (63%) developed grade 1 (G1) PN at a

median of 5 cycles (range, 3.5 – 11); 3/8 (37%) patients developed G2

PN at a median of 18 cycles (range, 13‐19). Median time of PN re-

covery from G2 to G1 is 1.6 mon; median recovery from PN G1 to

resolution is 6.1 mon. Additional BV‐related adverse events seen in

>10% of patients included increased ALT (G1, n = 4), increased AST

(G1, n = 3; G2, n = 1), diarrhea (G1, n = 3), fatigue (G1, n = 2; G2, n =

1); infusion‐related reaction (G1, n = 3; G2, n = 1), localized edema

(G1, n = 2), maculopapular rash (G1, n = 1; G2, n = 1; G3, n = 1), pain

in extremity (G2, n = 2), pruritus (G1, n = 2; G3, n = 1) and nausea

(G1, n = 2).

Conclusion: Treatment with BV at 0.9 mg/kg resulted in an ORR of

42% (95% CI, 20‐66%) which did not meet the primary efﬁcacy

endpoint. However, we observed a lower rate of ≥G2 PN than re-

ported with full dose therapy in ALCANZA. We are now enrolling BV‐

naïve patients in Cohort 1 for treatment with BV at 1.2 mg/kg. We

are also enrolling patients in an exploratory cohort of patients pre-

viously treated with BV, and a second exploratory cohort of patients

with LyP. We continue to collect correlative data on HRQoL, PN and

the tumor microenvironment.

The research was funded by: Seattle Genetics

Keywords: Cutaneous non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

FIGURE 1 Swimmer's plot. 1A indicates response of MF patients in Cohort 1

SUPPLEMENT ABSTRACTS

295

N. Khan

Research funding: Seattle Genetics

S. Noor

Consultant or advisory role: Kyowa Kirin

S. Horwitz

Consultant or advisory role: Acrotech Biopharma, ADC Therapeutics,

Astex, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa

Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle

Genetics, Shoreline Bio, Takeda, Trillium Therapeutics, Tubulis,

Verastem, SecuraBio, and Vividion Therapeutics.

Research funding: ADC Therapeutics, Afﬁmed, Aileron, Celgene, Daii-

chi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda,

Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.

A. Moskowitz

Honoraria: Imbrium Therapeutics L.P, Janpix Ltd., Merck, Seattle

Genetics, and Takeda

Research funding: ADC Therapeutics, Miragen, Seattle Genetics,

Merck, Bristol‐Myers Squibb, and Incyte

212 | POPULATION‐BASED COHORT STUDY OF THE EFFICACY

OF BRENTUXIMAB‐VEDOTIN IN RELAPSED SYSTEMIC

ANAPLASTIC LARGE CELL LYMPHOMA USING PUBLIC HEALTH

ENGLAND DATA

S. Halligan

, M. J. Grainge

, N. Martinez‐Calle

, C. P. Fox

M. Bishton

Nottingham University Hospitals NHS Trust, School of Medicine,

Nottingham, UK,

University of Nottingham, Division of Epidemiology and

Public Health, School of Medicine, Nottingham, UK,

Nottingham

University Hospitals NHS Trust, Department of Haematology,

Nottingham, UK

Introduction: Systemic anaplastic large cell lymphoma (sALCL) is a T‐

cell lymphoma, historically associated with low cure rates following

relapse. Following a pivotal phase II study (Pro et al), the immuno‐

conjugate Brentuximab Vedotin (BV) became available in England

via the Cancer Drugs Fund (CDF) in 2013. To date, no large‐scale

population‐based studies have described outcomes following BV.

Public Health England (PHE) collects information on all cancer di-

agnoses in England, and since April 2012 all delivered Systemic Anti‐

Cancer Therapy (SACT). We aimed to evaluate whether routinely

collected PHE data can reliably assess outcomes of patients with

lymphoma.

Methods: We requested anonymised Ofﬁce of Data Release (ODR)

information on sALCL patients ≥18 years treated with BV mono-

therapy between 1

Jan 2014‐31

Dec 2019. We excluded primary

cutaneous and breast‐implant associated ALCL, patients in the

ECHELON‐2 trial and BV received in combination. We requested

baseline demographics, ALK protein status, dates of BV cycles, SACT

data prior to and following BV, and prior autologous/allogeneic stem

cell transplantation (SCT). Kaplan‐Meier survival methods were used

to compare the primary outcome of all‐cause mortality between

groups deﬁned by age, gender and ALK status in univariate analyses.

Results: 173 patients were identiﬁed, of whom 46 were excluded. The

ﬁnal cohort comprised 127 patients with r/r ALCL with a median age of

60 years at initiation of BV and median follow up time of 10 months. 49

(38.6%) patients were ALK + ve and 78 (61.4%) ALK‐ve. 106 (83.5%)

received BV second line, and 13 (10.2%) third or fourth line. 95 (74.8%)

received CHOP ﬁrst line. Based on SACT data 18 (14.2%) received SCT

in ﬁrst remission (16 auto, 2 allo). The median number of BV cycles

received was ﬁve. Median 2‐year overall survival (OS) was 46.6%. The

majority (59) of deaths occurred within the ﬁrst 18 months, followed by

a survival plateau with only four subsequent deaths. There was no

difference in OS between ALK+ve and ALK‐ve (p = 0.78), age <40 vs

≥40 years(p = 0.89), age <60 vs ≥60(p = 0.96), between genders(p =

0.25), or receiving prior SCT (p = 0.55). Two patients received SCT after

BV, with both alive 18+ months post‐transplant. Receiving BV as

second line therapy was associated with improved survival, with 2‐year

OS of 50.3% versus 29.7% for those third or fourth line (p = 0.03).

Conclusions: We conﬁrm BV is a highly effective treatment for r/r

sALCL with real world survival outcomes across sub‐groups highly

comparable with clinical trial data. Study weaknesses include lack of

information on toxicity and data from double blind studies, although

this data is now being collected. Analysis of routinely collected PHE

data offers the opportunity to undertake high quality, nationwide

population‐based studies, to inform the efﬁcacy of high‐cost drugs

such as BV in routine clinical practice.

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma,

Immunotherapy

No conﬂicts of interest pertinent to the abstract.

213 | PHASE 1 RESULTS OF ANTI‐PD‐LIGAND 1

(DURVALUMAB) & LENALIDOMIDE IN PATIENTS WITH

CUTANEOUS T CELL LYMPHOMA AND CORRELATION WITH

GENE EXPRESSION PROFILE

C. S. Querfeld

, N.‐C. Tsai

, J. Palmer

, X. Martinez

, F. Abdulla

, X.

, S. T. Rosen

, J. Zain

City of Hope, Beckman Research Institute and Dept. of Pathology,

Duarte, California, USA,

City of Hope, Division of Biostatistics, Duarte,

296

SUPPLEMENT ABSTRACTS

California, USA,

City of Hope, Division of Biostatistics, Duarte, California,

USA,

City of Hope, Division of Dermatology, Duarte, California, USA,

City of

Hope, Integrative Genomics Core, Duarte, California, USA,

City of Hope,

Hematology and Hematopoietic Cell Transplantation, Duarte, California,

USA,

City of Hope, Hematology and Hematopoietic Cell Transplantation,

Duarte, California, USA

Background: T cells in CTCL are functionally exhausted, charac-

terized by the expression of immune inhibitory molecules (Cancer

Immunol Res 6; 2018). These ﬁndings justify the evaluation of

immune checkpoint inhibition to reverse T cell exhaustion in CTCL.

We initiated a phase 1/2 clinical trial of lenalidomide and durva-

lumab (NCT03011814) to determine the safety and efﬁcacy of this

regimen. Durvalumab is a human monoclonal antibody with high

afﬁnity and selectivity for PD‐L1, targeting exhausted T cells and

distinct cells within their environment. Lenalidomide, an oral

immunomodulatory drug (IMiD) has previously shown activity in

CTCL (Blood 123; 2014). Durvalumab may restore an anti‐tumor

immune response, and the combination of durvalumab/lenalido-

mide may enhance immune checkpoint blockade‐induced immune

responses.

Methods: Pts were enrolled in sequential cohorts to receive durva-

lumab (ﬁxed dose at 1500 mg) and dose escalation of lenalidomide

(dose level 1 = 10 mg for all cycles; dose level 2 = 10 mg for cycle 1,

15 mg for all subsequent cycles; dose level 3 = 10 mg for cycle 1, 15

mg for cycle 2, and 20 mg for all subsequent cycles) to characterize

safety, efﬁcacy and antitumor activity. Serial skin samples were

collected to assess the impact on tumor cells and tumor

microenvironment.

Results: 10 males/3 females, median age 36 (29–72 y), with aggres-

sive or refractory/advanced CTCL, clinical stages IB (2), IIA (3), IIB (6),

IIIA (1), and aggressive epidermotropic CD8 + CTCL (1) and a median

of prior systemic treatments of 3 (range, 2‐8) were enrolled. Dose

level 1 (n = 3), dose level 2 (n = 3), dose level 3 (n = 4). Median follow

up time was 16.1 months (range, 3.7‐36.1) months. No serious AEs or

DLTs were observed during the DLT evaluation period (cycles 1‐3).

The most frequently reported AEs were fatigue (n = 8), skin pain (n =

4), chills (n = 3), anemia (n = 3), and leukopenia (4). One grade 3

maculopapular rash (possibly due to lenalidomide) was observed, all

other treatment‐related AEs were grade 1/2 in severity. One pt

discontinued treatment due to fatigue. Three pts developed grade 1/

2 autoimmune thyroiditis that resolved with treatment. Median cy-

cles of treatment were 7 (range, 1‐28). Median duration of response

was 6 (range, 1‐ 28+) months. Nine pts achieved PR, 2 pts maintained

stable disease and 2 pts developed PD. Three pts remain on treat-

ment. Gene expression levels for several checkpoints were analyzed.

Conclusions: Anti‐PD‐L1/lenalidomide has signiﬁcant clinical activity

in refractory/advanced CTCL, which will be formally evaluated in the

Phase 2 portion. Responses were durable and ongoing, and treatment

was well tolerated. Dose escalation is up to maximum dose of 20 mg

lenalidomide daily. Our preliminary results reveal adaptive and

innate immune signatures that may be predictive of response to

checkpoint blockade and yield insights into mechanisms of thera-

peutic resistance.

The research was funded by: This research was funded in part

through an NIH/NCI Cancer Center Support Grant (P30CA033572)

to City of Hope, NIH/NCI grant (R01 CA229510‐01) to C. Querfeld

and Leukemia Lymphoma Society Clinical Scholar Award to C.

Querfeld

Keywords: Immunotherapy, Targeting the Tumor Microenvironment

Conﬂicts of interests pertinent to the abstract

C. S. Querfeld

Consultant or advisory role: Helsinn, Kyowa Kirin, Bioniz, Miragen,

Trillium

Research funding: Celgene

214 | ROMIDEPSIN AND CARFILZOMIB IN RELAPSED /

REFRACTORY PERIPHERAL T‐CELL LYMPHOMA WITH

ASSESSMENT OF H23B AS A PREDICTIVE BIOMARKER – THE UK

NCRI SEAMLESS PHASE 1/2 ROMICAR TRIAL

G. P. Collins

, S. Booth

, L. R. Cherrill

, D. Slade

, C. Morland

L. Hopkins

, E. Nagy

, K. Linton

, C. P. Fox

, D. Lewis

, A. Davies

G. Turner

, G. Rees

, C. Yap

, K. Cwynarski

NIHR Oxford Biomedical Research Centre, Churchill Hospital,

Haematology, Oxford, UK,

Churchill Hospital, Clinical Haematology,

Oxford, UK,

Birmingham University, Cancer Research UK Clinical Trials

Unit, Birmingham, UK,

Christie Hospital, Medical onology, Manchester,

UK,

Nottingham University Hospitals NHS Foundation Trust,

Haematology, Nottingham, UK,

Plymouth Hospitals NHS Trust,

Haematology, Plymouth, UK,

University of Southampton, CRUK/NIHR

Experimental Cancer Medicines Centre, Southampton, UK,

Oxford

University Hospitals NHS Foundation Trust, Cellular Pathology, Oxford,

UK,

Institute of Cancer Research, Clinical Studies, London, UK,

University College London Hospitals NHS Foundation Trust,

Haematology, London, UK

Introduction: Relapsed/refractory Peripheral T‐cell lymphoma

(PTCL) has poor outcomes. The histone deacetylase inhibitor

(HDACi) romidepsin (ROMI) has a reported overall response rate

(ORR) of 25%, median progression free survival (PFS) of 4 months

and some long‐term responses. Carﬁlzomib (CAR) is a proteasome

inhibitor synergising with HDACis in a number of cancer cell lines.

HR23B expression is hypothesised to be a predictive biomarker of

HDACi response based on in vitro data suggesting it is required for

cancer cell lethality. The RomiCar trial aimed to determine the

maximum tolerated dose (MTD) of the combination of ROMI and

CAR and the best ORR over the ﬁrst 8 cycles with assessment of

HR23B as a predictive biomarker.

Methods: Phase (Ph) 1 used the continual reassessment method

(CRM) to determine the MTD of ROMI with CAR deﬁned as the dose

closest to 25% probability of occurrence of a dose limiting toxicity

SUPPLEMENT ABSTRACTS

297

(DLT) during cycle 1. Six dose levels were planned. The CRM design

allowed more rapid accrual: once the maximum 3 patients were on

the dose level under evaluation, further patients received the dose

level below, with all data contributing to dose decisions. Ph 2 used a

single stage A’Hern design to assess best ORR during the ﬁrst 8

cycles (assessed using the Revised Response Criteria for Malignant

Lymphoma) of the combination in all participants (pts) treated at the

MTD. ROMI was given IV on days 1, 8 and 15 of a 28d cycle; CAR IV

on days 1, 2, 8, 9, 15 and 16. HR23B expression was performed on

formalin ﬁxed parafﬁn embedded tissue.

Results: 33 pts enrolled to Ph 1 with 27 evaluable for MTD assess-

ment. 34 pts were treated at the MTD and evaluable for Ph 2. Me-

dian age 62y (22‐82y); 69% male; median prior treatment lines 2

performance status 0 (44%), 1 (44%) or 2 (10%) (1 unknown); 53%

refractory to last treatment. 51% had PTCL Not Otherwise Speciﬁed;

40% angioimmunoblastic T‐cell lymphoma. 7 DLTs were seen in 6

patients during phase 1. The MTD was deﬁned as ROMI 10 mg/m

with CAR 20mg/m

for 2 doses then 40mg/m

, giving an estimated

posterior DLT probability of 0.216 with a 90% credible interval

(0.106, 0.352). The ORR at the MTD was 32% (95% conﬁdence in-

terval 19‐49%): 15% complete response, 18% partial response, 18%

stable disease. Grade 3/4 adverse events in ≥ 10% pts were anaemia

(17%); neutropenia (35%); thrombocytopenia (42%). Median PFS was

4.0 months (median follow up 19 months); 4 participants remain on

treatment. HR23B expression was not associated with response with

27% (3 of 11) HR23B positive pts responding.

Conclusion: The combination of ROMI and CAR is safe and tolerable

in R/R PTCL with MTD declared efﬁciently by a ﬂexible CRM trial

design. Treatment at the MTD gave an ORR of 32% and median PFS

of 4.0 months which was similar to the ROMI phase 2 trial. HR23B

expression did not appear to be associated with response and R/R

PTCL remains a signiﬁcant area of unmet need.

The research was funded by: Blood Cancer UK, BMS and Amgen

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

G. P. Collins

Consultant or advisory role: Celgene, a Bristol Myers Squibb

company

Honoraria: Celgene, a Bristol Myers Squibb company

Research funding: Celgene, a Bristol Myers Squibb company and

Amgen

K. Linton

Consultant or advisory role: Celgene, a Bristol Myers Squibb

Company

Honoraria: Celgene, a Bristol Myers Squibb Company

C. P. Fox

Consultant or advisory role: Celgene, a Bristol Myers Squibb

company

Honoraria: Celgene, a Bristol Myers Squibb company

Educational grants: Celgene, a Bristol Myers Squibb company

A. Davies

Consultant or advisory role: Celgene, a Bristol Myers Squibb

company

Honoraria: Celgene, a Bristol Myers Squibb company

Research funding: Celgene, a Bristol Myers Squibb company

Educational grants: Celgene, a Bristol Myers Squibb company

K. Cwynarski

Consultant or advisory role: Celgene, a Bristol Myers Squibb

company

Honoraria: Celgene, a Bristol Myers Squibb company

Educational grants: Celgene, a Bristol Myers Squibb company

215 | SINTILIMAB PLUS CHIDAMIDE FOR RELAPSED/

REFRACTORY (R/R) EXTRANODAL NK/T CELL LYMPHOMA

(ENKTL): A PROSPECTIVE, MULTICENTER, SINGLE‐ARM, PHASE

IB/II TRIAL (SCENT)

H. Huang

, Y. Gao

, X. Wang

, B. Bai

, L. Zhang

, Y. Xiao

, X. Liu

W. Li

, Q. Cai

, Z. Li

, Y. Chen

, W. Xu

, R. Feng

, H. Wu

, J. Li

X. Wu

Sun Yat‐sen University Cancer Center, Department of Medical Oncology,

Guangzhou, China,

Union Hospital afﬁliated to Tongji Medical College of

Huazhong University of Science and Technology, Cancer Center,

Wuhan, China,

Guangdong General Hospital, Guangdong Academy of

Medical Sciences, Department of lymphoma, Guangzhou, China,

Guangdong General Hospital, Guangdong Academy of Medical Sciences,

Department of pathology, Guangzhou, China,

the First Afﬁliated Hospital

of Nanjing Medical University, Jiangsu Province Hospital, Department of

Hematology, Nanjing, China,

Nanfang Hospital, Southern Medical

298

SUPPLEMENT ABSTRACTS

University, Department of Hematology, Guangzhou, China,

Hubei Cancer

Hospital afﬁliated to Huazhong University of Science and Technology,

Department of lymphoma, Wuhan, China,

Sun Yat‐sen University Cancer

Center, Department of Clinical Research, Guangzhou, China,

Geneseeq

Technology Inc., Translational Medicine Research Institute, Toronto,

Canada

Background: Patients with r/r ENKTL have a poor prognosis after

failing asparaginase based regimen, and there is lack of effective

treatment. ORIENT‐4 trial demonstrated Sintilimab (a fully human

anti‐PD‐1 antibody) was effective and well tolerated in r/r ENKTL(J

Clin Oncol 37, 2019 (suppl; abstr 7504)). Chidamide, an oral

subtype‐selective histone deacetylase inhibitor (HDACi) showed

efﬁcacy for r/r ENKTL. Moreover, accumulating evidences have

shown the synergism between histone deacetylase inhibitor and

anti‐PD‐1 antibody. This trial was designated to evaluate the efﬁ-

cacy and safety of the novel combination of Sintilimab plus Chida-

mide in r/r‐ENKTL.

Methods: This study enrolled patients with histologically conﬁrmed

r/r‐ENKTL failed from asparaginase‐based regimen. In Phase Ib, a

standard “3+3” design was utilized to identify the MTD, DLT and

recommended Phase II dosage (RP2D) of Chidamide plus Sintili-

mab. In phase II, patients received Sintilimab (200mg) plus Chi-

damide (RP2D) every 21 days for up to 1 year or until PD,

intolerable toxicity, withdrawal of consent. The primary endpoint

was ORR assessed by investigators per RECIL 2017 criteria (NCT

03820596).

Results: From March 2019 to January 2021, 38 eligible patients

were enrolled in China. Of 37 response evaluable patients, 22

patients (59.5%) achieved an ORR including 18 (48.6%) patients

with CR (Figure 1). With median follow‐up time of 12.7 months

(range, 0.9 to 21.5), the median TTR was 6.0 weeks (range, 5.0

to12.4) and median DOR was 13.3+ months (range, 1.3 to 19.2+,

Figure 2). Estimated 18 months OS and PFS rate were 76.2% ±

6.9%, and 52.5% ± 8.7%, respectively. OS and PFS for patients

with CR/PR were superior to SD/PD (P < 0.001, Figure 3). We

assessed PD‐L1 (22C3) expression by combined positivity score

(CPS). The median CPS was 40.0, patients with CPS ≥ 30 exhibited

FIGURE 2 Treatment exposure and

response duration(n=38)

FIGURE 1 Best change in the SPD of target lesions from

baseline for all patients in the evaluable set(n=37)

SUPPLEMENT ABSTRACTS

299

beneﬁt more from the combination than their counterparts with

CPS < 30. Both ctDNA and EBV‐DNA clearance had promising

predictive value for survival. Twenty‐ﬁve (65.8%) patients reported

TRAEs. The most frequently observed (≥10%) TRAEs were

neutropenia (65.8%), thrombocytopenia (44.4%), anemia (44.4%),

hypothyroidism (47.4%), hypoproteinemia (36.8%), transaminase

increased (26.3%), nausea and vomiting (26.2%). The most frequent

Grade (G) ≥3 TRAEs were neutropenia (28.9%), thrombocytopenia

(10.5%). Immune‐related AEs were reported in 18 (47.4%) pa-

tients including a G4 exfoliative dermatitis and an interstitial

pneumonia. TEAEs that led to permanent treatment discontinua-

tion occurred in two (5.3%) patients. No death was related to the

study drug.

Conclusion: Sintilimab combined with Chidamide showed manage-

able safety proﬁle and yielded effective antitumor activity, durable

response in patients with r/r ENKTL for the ﬁrst time. It is a prom-

ising therapeutic option for this population, especially for those with

CPS ≥ 30. The combination of PD‐1 antibody and HDACi may rep-

resents a novel strategy for r/r ENKTL. Further investigation is

warranted.

The research was funded by: Innovent Biologics Inc.

Keywords: Immunotherapy, Aggressive T‐cell non‐Hodgkin lym-

phoma, Extranodal non‐Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

216 | A PHASE I

STUDY OF AN ORAL PI3Kδ INHIBITOR

LINPERLISIB IN PATIENTS WITH RELAPSED OR REFRACTORY

PERIPHERAL T CELL LYMPHOMA

L. Qiu

, J. Jin

, H. Cen

, K. Zhou

, X. Xu

, F. Li

, T. Wu

, H. Yang

, Z.

Wang

, Z. Li

, H. Bao

, Z. Xu

, Y. Shu

Blood Institute of the Chinese Academy of Medical Sciences,

lymphoma treatment center, Tianjin, China,

First Hospital Afﬁliated

Zhe Jiang Medical University, Department of Hematology, Hangzhou,

China,

Guangxi Medical University Afﬁliated Tumor Hospital,

Department of Medical Oncology, Nanning, China,

Henan Cancer

Hospital, Department of Hematology, Zhengzhou, China,

Cancer

Hospital afﬁliated to Nantong University, Department of Hematology

and Lymphoma, Nantong, China,

The First Afﬁliated Hospital of

Nanchang University, Department of Hematology, Nanchang, China,

Guizhou Cancer Hospital, Department of Lymphoma, Guiyang, China,

Cancer Hospital of The University of Chinese Academy of Sciences,

Department of Lymphoma, Hangzhou, China,

Linyi Cancer Hospital,

Department of Medical Oncology, Linyi, China,

Sun Yat‐Sen Univer-

sity Cancer Center, Department of Medical Oncology, Guangzhou,

China,

Shanghai Yingli Pharmaceutical Co., Ltd, Clinical Management

Department, Shanghai, China,

Shanghai Yingli Pharmaceutical Co.,

Ltd, Clinical Management Department, Shanghai, China,

Shanghai

Yingli Pharmaceutical Co., Ltd, Clinical Management Department,

Shanghai, China

FIGURE 3 OS and PFS. (A)OS of whole cohort. (B)PFS of whole cohort. (C)OS of CR/PR vs SD/PD. (D)PFS of CR/PR vs SD/PD

300

SUPPLEMENT ABSTRACTS

Background: Linperlisib is an oral highly selective small molecule

inhibitor of PI3Kδ that is well‐tolerated with a favorable PK proﬁle in

patients with lymphomas and advanced solid tumors. This phase I

study is evaluating the efﬁcacy and safety of Linperlisib in relapsed or

refractory peripheral T‐cell lymphoma (PTCL), a highly aggressive

malignancy with few treatment options for patients.

Methods: Eligible PTCL patients that had received at least 1 prior

systemic therapy were administered Linperlisib 80mg orally once

daily (RP2D) in 28 day cycles until disease progression, unacceptable

toxicity, or withdrawal from the study. Tumor response was assessed

by IWG 2007 criteria with CT performed every 2 cycles. The primary

endpoint was the overall response rate (ORR), and the secondary

endpoint was toxicity assessed by NCI‐CTCAE5.0.

Results: As of March 5

, 2021, 38 PTCL patients were enrolled in

this exploratory trial. Most patients were stage III (39.5%) or IV

(52.6%). Of the 30 evaluable patients, the PTCL histologies were

PTCL‐NOS (n = 13), AITL (n = 11), ALCL (n = 3), NKTCL (n = 2) and

MEITL (n = 1). With the 30 evaluable patients, 21 had Investigator

conﬁrmed responses for a 70% ORR, including 33.3% CR (10 pt) and

36.7% PR (11 pt). In two of the major subtypes, ORR was 46.2% (6/

13) PTCL‐NOS and 81.8% (9/11) AITL, respectively. Most responses

occurred by ﬁrst assessment at C2D28. A disease control rate of

100% was observed, and 24 patients (80% of evaluable patients) are

still receiving linperlisib treatment, with 8 patients >6 cycles of

follow‐up to date. 36 patients experienced at least 1 TRAE in the

trial, with 94.6% of AEs ≤ grade 2. There were no unexpected tox-

icities, consistent with other lymphoma patients who had been

treated with linperlisib previously. The most common TRAEs (≥10%

all grades) were neutrophil count decreased (57.9%), leukocyte count

decreased (36.8%), hypertriglyceridemia (21.1%), aspartate amino-

transferase increased (15.8%), hypercholesterolemia (15.8%), alanine

aminotransferase increased (15.8%), creatinine increased (10.5%),

rash (10.5%), platelet count decreased (10.5%) and electrocardio-

gram T wave abnormal (10.5%). No AE grade 4 was observed, and

AEs grade 3 were neutrophil count decreased (10.5%), leukocyte

count decreased (2.6%), stomatitis (2.6%), platelet count decreased

(2.6%), pneumonia (2.6%) and blood lipase increased (2.6%). 7 pa-

tients (18.4%) experienced at least one SAE, in which 5 (13.2%) SAEs

were considered to be drug‐related, including neutrophil count and

leukocyte count decreased (1), gastritis (1), and pneumonia (3).

Conclusion: Linperlisib showed signiﬁcant activity in r/r PTCL pa-

tients and was well tolerated with manageable toxicities. With these

promising ﬁndings, further study of the treatment of PTCL by Lin-

perlisib is warranted. Clinical Trial Information: NCT04108325.

Sponsor: Shanghai Yingli Pharmaceutical.

EA – previously submitted to ASCO 2021.

The research was funded by: Shanghai Yingli Pharmaceutical Co., Ltd

Keywords: Molecular Targeted Therapies

Conﬂicts of interests pertinent to the abstract

H. Bao

Employment or leadership position: Chief medical ofﬁcer

Z. Xu

Employment or leadership position: general manager

Y. Shu

Employment or leadership position: Associate Chief Medical Ofﬁcer

217 | IMPACT OF RITUXIMAB ON TREATMENT OUTCOMES OF

PATIENTS WITH ANGIOIMMUNOBLASTIC T‐CELL LYMPHOMA;

A POPULATION‐BASED ANALYSIS

F. O. Meeuwes

, M. Brink

, M. W.M. van der Poel

, M. J. Kersten

Mariël. Wondergem

, P. G.N.J. Mutsaers

, L. H. Böhmer

S. Woei‐A‐Jin

, O. Visser

, R. Oostvogels

, P. M. Janssen

G. A. Huls

, J. S.P. Vermaat

, M. Nijland

Martini Hospital, Department of Hematology, Groningen, Netherlands,

Netherlands Comprehensive Cancer Organisation (IKNL), Department of

Research and Development, Utrecht, Netherlands,

Maastricht University

Medical Center, Department of Hematology, Maastricht, Netherlands,

Amsterdam University Medical Centers, Department of Hematology,

Amsterdam, Netherlands,

Erasmus MC, Department of Hematology,

Rotterdam, Netherlands,

Haga Ziekenhuis, Department of Hematology,

The Hague, Netherlands,

UZ Leuven, Department of Hematology, Leuven,

Belgium,

Isala Hospital, Department of Hematology, Zwolle, Netherlands,

University Medical Center Utrecht, Department of Hematology, Utrecht,

Netherlands,

Leiden University Medical Center, Department of

Pathology, Leiden, Netherlands,

University Medical Center Groningen,

Department of Hematology, Groningen, Netherlands,

Leiden University

Medical Center, Department of Hematology, Leiden, Netherlands

Introduction: Angioimmunoblastic T‐cell lymphoma (AITL) is a

mature T‐cell malignancy that is often accompanied by paraneo-

plastic phenomena due to immune deregulation. Patients are treated

with cyclophosphamide, doxorubicin, vincristine, and prednisone with

or without etoposide (CHO(E)P) followed by high dose chemotherapy

in younger patients. In the majority of patients, EBV‐positive, CD20‐

positive B‐cells are present in the tumor inﬁltrate. It has been

postulated that targeting these B‐cells with the anti‐CD20 mono-

clonal antibody rituximab might improve outcome, but this has only

been studied in small series. This nationwide, population‐based study

evaluated the impact of rituximab on best response and overall

survival (OS) of patients with AITL treated with CHO(E)P.

Methods: All patients with AITL diagnosed between 2014‐2018 and

treated with at least one cycle of CHO(E)P with or without rituximab

were identiﬁed in the Netherlands Cancer Registry (NCR), with

survival follow‐up through February 1, 2021. Baseline characteristics,

best response and survival outcomes were collected. OS was deﬁned

as the time from AITL diagnosis to all‐cause‐death. Multivariable

analysis of OS was performed using Cox regression.

Results: Overall, 237 patients with AITL received CHO(E)P (median

age, 66 years; 62% male; 97% stage II‐IV). Rituximab was added to

CHO(E)P in 100 patients (42%). Similar mean age and Ann Arbor

stage were found in patients treated with CHO(E)P and R‐CHO(E)P.

SUPPLEMENT ABSTRACTS

301

There was a predominance of female patients in the CHO(E)P group

as compared to the R‐CHO(E)P group (45% vs. 30%, P = 0.023). For

both the CHO(E)P and the R‐CHO(E)P group, the proportion of pa-

tients who received etoposide (30% vs. 33%; P = 0.702) and

consolidation with an autologous stem cell transplantation (ASCT)

(29% for both) was comparable. The best overall response (complete

remission and partial remission) rate for patients who received CHO

(E)P and R‐CHO(E)P was 73% and 82%, respectively (P = 0.105;

Figure 1‐A). The median follow up was 52.3 months. The 5‐year OS

were 46% and 43% for patients who received CHO(E)P or R‐CHO(E)

P (P = 0.822, Figure‐1B), respectively. Age, sex, and addition of

etoposide and/or rituximab to CHOP were not associated with OS.

Consolidation with ASCT, however, signiﬁcantly improved prognosis

(Hazard ratio 0.25, 95% conﬁdence interval 0.14‐0.43; P < 0.001).

Conclusion: In this large cohort of patients, the addition of rituximab

to CHO(E)P did not improve OS. To our knowledge, this study reports

the largest nationwide and population‐based cohort published on this

subject thus far.

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

218 | ROMIDEPSIN‐CHOEP PLUS UP‐FRONT STEM‐CELL

TRANSPLANTATION IN PERIPHERAL T‐CELL LYMPHOMA (PTCL):

FIRST ANALYSIS OF THE PHASE II FIL‐PTCL13 STUDY

A. Chiappella

, C. Carniti

, A. Re

, C. Castellino

, A. Evangelista

R. Ciancia

, L. Orsucci

, A. Pinto

, S. V. Usai

, A. Arcari

, F. Ilariucci

F. G. Rossi

, F. Benedetti

, L. Flenghi

, C. Ghiggi

, A. L. Molinari

V. Stefoni

, S. Volpetti

, V. R. Zilioli

, F. Ballerini

, R. Bruna

F. Cavallo

, G. Musuraca

, C. Patti

, F. Re

, M. Tani

M. Varettoni

, M. Zanni

, A. Dodero

, S. A. Pileri

, G. Ciccone

P. Corradini

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Hematology

and Stem Cell Transplantation, Milano, Italy,

Fondazione IRCCS, Istituto

Nazionale dei Tumori di Milano, Laboratory of Hematology, Division of

Hematology and Stem Cell Transplantation, Milano, Italy,

ASST Spedali

Civili di Brescia, Hematology Division, Brescia, Italy,

Azienda Ospedaliera

S. Croce e Carle, Division of Hematology, Cuneo, Italy,

Azienda

Ospedaliera e Universitaria Città della Salute e della Scienza and CPO

Piemonte, Unit of Clinical Epidemiology, Torino, Italy,

Centro di

Riferimento Oncologico (CRO) IRCCS, Onco‐hematology and Stem Cell

Transplantation and Cellular Therapies, Aviano, Italy,

Azienda Ospeda-

liera e Universitaria Città della Salute e della Scienza, Division of Hema-

tology, Torino, Italy,

Istituto Nazionale Tumori, Fondazione G. Pascale,

IRCCS, Hematology‐Oncology & Stem Cell Transplantation Unit, Napoli,

Italy,

Ospedale Oncologico Armando Businco, Hematology, Cagliari, Italy,

Ospedale Guglielmo da Saliceto, Hematology Unit, Piacenza, Italy,

Azienda USL‐IRCCS, Hematology, Reggio Emilia, Italy,

Fondazione

IRCCS Cà Granda, OM Policlinico, Division of Hematology, Milano, Italy,

Azienda Ospedaliera Universitaria di Verona, Hematology and Stem Cell

Transplantation, Verona, Italy,

Azienda Ospedaliera di Perugia, Hema-

tology, Perugia, Italy,

IRCCS Ospedale Policlinico San Martino, Hema-

tology, Genova, Italy,

Ospedale degli Infermi, Hematology, Rimini, Italy,

University of Bologna, Institute of Hematology “Seràgnoli”, Bologna,

Italy,

Presidio Ospedaliero Universitario “Santa Maria della Miser-

icordia” di Udine, ASUFC, Clinic of Hematology, Udine, Italy,

ASST

Grande Ospedale Metropolitano Niguarda, Division of Hematology,

Milano, Italy,

IRCCS Ospedale Policlinico San Martino, Clinic of He-

matology, Genova, Italy,

Ospedale Maggiore Della Carità, Division of

Hematology, Novara, Italy,

University of Torino; Azienda Ospedaliera e

Universitaria Città della Salute e della Scienza, Division of Hematology,

Department of Molecular Biotechnologies and Health Sciences, Torino,

Italy,

IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino

Amadori”, Division of Hematology, Meldola, Italy,

Azienda Villa Soﬁa

Cervello, Division of Onco‐Hematology, Palermo, Italy,

Azienda

Ospedaliera‐Universitaria di Parma, Hematology and CTMO, Parma, Italy,

Ospedale Santa Maria delle Croci, Hematology Unit, Ravenna, Italy,

Fondazione IRCCS Policlinico San Matteo, Division of Hematology,

Pavia, Italy,

Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo,

Division of Hematology, Alessandria, Italy,

European Institute of

302

SUPPLEMENT ABSTRACTS

Oncology IRCCS, Division of Haematopathology, Milano, Italy,

Chair of

Hematology, University of Milano; Fondazione IRCCS Istituto Nazionale

dei Tumori di Milano, Division of Hematology and Stem Cell Trans-

plantation, Milano, Italy

Introduction: Peripheral T‐cell lymphomas (PTCL) are a rare disease

with a poor prognosis, even when treated with high dose chemo-

therapy and stem cell transplantation (HDC + SCT). Romidepsin (Ro),

a histone deacetylase inhibitor, showed activity in relapsed or re-

fractory PTCLs, with a good proﬁle of safety.

Methods: In the phase Ib FIL‐PTCL13 (NCT02223208), we tested

the combination of Ro with cyclophosphamide, doxorubicin, eto-

poside, vincristine, dexamethasone (CHOEP) plus HDC + SCT in

young PTCLs patients eligible to transplant, and we deﬁned 14

mg/ms the maximum tolerated dose of Ro. Aim of the phase II

part of the study was to evaluate the efﬁcacy (response rate,

progression free survival, PFS, at 18‐months and overall survival,

OS) of Ro‐CHOEP followed by HDC + SCT. The primary objective

of the study was to demonstrate a 15% increase in 18‐months PFS

for the combination Ro‐CHOEP plus HDC + SCT, compared to the

literature data (from 55% to 70%, planned sample size = 110).

Patients aged 18‐65 eligible to SCT, with advanced PTCL‐NOS,

angioimmunoblastic/T‐helper follicular and ALK negative anaplastic

large cell lymphoma were eligible. Treatment plan consisted of 6

courses of Ro‐CHOEP every 21 days (14 mg/ms Ro day 1 and 8),

followed by cisplatin‐cytarabine‐dexamethasone (DHAP) with stem

cell harvest and SCT. Patients in complete response (CR) after

induction proceeded to autoSCT, while those in partial response

(PR), with an available HLA‐matched donor, proceeded to alloSCT

upfront.

Results: From September 2017 to October 2020, 83 patients were

enrolled into the phase II part of the study; median age was 55

years (IQR 49;59); 74 (89%) had stage III‐IV and 29 (35%) IPI risk

>2. An interim analysis was performed, according to the statistical

plan, when the ﬁrst 75 patients were enrolled. At a median

follow‐up of 12 months, the estimated 18‐months PFS was 53%

(95% CI: 0.39‐0.64) and the OS was 79% (95% CI: 0.66‐0.87). On

74 patients evaluable for response after induction, the overall

response rate (ORR) after 6 Ro‐CHOEP was 72% (53 patients),

with 59% (44 patients) complete response (CR). On 65 patients

evaluable for end of treatment response, the ORR after SCT was

42/65 (65%), with 36 (55%) CR. The most frequent toxicities

during Ro‐CHOEP treatment were hematological, with grade 3‐4

neutropenia and thrombocytopenia in 35% and 37% of cycles,

respectively.

Conclusions: The interim analysis demonstrated an 18‐months PFS

of 53%; based on these results, which demonstrated a PFS super-

imposable to those obtained with conventional HDC+SCT, the

enrollment was stopped. In conclusion, the addition of Romidepsin to

CHOEP did not ameliorate prognosis in newly diagnosis PTCLs

eligible to SCT.

The research was funded by: Romidepsin was provided free by

Celgene.

Keywords: Chemotherapy, Combination Therapies, Stem Cell

Transplant

No conﬂicts of interest pertinent to the abstract.

219 | FRONTLINE BRENTUXIMAB VEDOTIN AND CHP (A

+CHP) IN PATIENTS WITH PERIPHERAL T‐CELL LYMPHOMA

WITH LESS THAN 10% CD30 EXPRESSION (SGN35‐032, TRIAL IN

PROGRESS)

D. Jagadeesh

, S. Knowles

, S. M. Horwitz

Cleveland Clinic Taussig Cancer Institute and Case Comprehensive

Cancer Center, Hematology and Medical Oncology, Cleveland, Ohio, USA,

Seagen Inc., Late Stage Development, Bothell, Washington, USA,

Memorial Sloan Kettering Cancer Center, Lymphoma Service, New York,

New York, USA

Introduction: In the ECHELON‐2 phase 3 clinical trial, brentuximab

vedotin, a CD30‐directed antibody‐drug conjugate, combined with

cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed

efﬁcacy in patients (pts) with peripheral T‐cell lymphoma (PTCL)

across a range of CD30 expression levels, including the lowest

eligible level of 10% by IHC.

It is expected that A+CHP will demonstrate efﬁcacy in PTCL

with <10% CD30 expression because: i) clinical responses to bren-

tuximab vedotin occurred in pts with low and undetectable CD30

expression (Jagadeesh 2019); and ii) the activity of CHP chemo-

therapy in PTCL is unrelated to CD30 expression. This study will

include subjects with PTCL subtypes other than systemic anaplastic

large cell lymphoma (sALCL).

Methods: This is a dual‐cohort, open‐label, multicenter, phase 2

clinical trial (EudraCT 2020‐002336‐74) designed to evaluate the

efﬁcacy and safety of A+CHP in subjects with non‐sALCL PTCL and

CD30 expression <10% on tumor cells. Up to approximately 40

subjects will be enrolled in each of the CD30 negative (expression

<1%) and the CD30 positive (expression ≥1% to <10%) cohorts. Only

subjects with CD30 expression <10% per central conﬁrmation will be

analyzed for the primary and secondary endpoints. Subjects will

receive 21‐day cycles of A+CHP for a target of 6‐8 cycles.

The primary endpoint of this trial is objective response rate

(ORR) per blinded independent central review (BICR) using the

Revised Response Criteria for Malignant Lymphoma (Cheson 2007).

Key secondary endpoints include complete remission (CR) and

progression‐free survival (PFS) per BICR and overall survival.

Key inclusion criteria include adults with newly diagnosed PTCL,

excluding sALCL, per the WHO 2016 classiﬁcation; CD30 expression

<10% by local assessment; and FDG‐avid disease by PET and

measurable disease of at least 1.5 cm by CT, as assessed by the site

radiologist.

Lymphoma response and progression will be assessed by BICR

per Cheson 2007 and modiﬁed Lugano criteria (Cheson 2014). A PET

scan is required at baseline, after Cycle 4, and after the completion of

SUPPLEMENT ABSTRACTS

303

study treatment. Follow‐up restaging CT scans will be performed

over the next two years.

Efﬁcacy and safety endpoints will be summarized with

descriptive statistics by cohort, for both the CD30 negative and

the CD30 positive cohorts. Time‐to‐event endpoints, such as PFS,

will be estimated using Kaplan‐Meier methodology and Kaplan‐

Meier plots will be presented. Medians for time‐to‐event ana-

lyses (eg, median PFS),will be presented and two‐sided 95% con-

ﬁdence intervals will be calculated using the log‐log transformation

method.

The trial currently is open at sites in the US. Sites in Europe are

expected to open in early 2021.

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: Seagen Inc.

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma, Combination

Therapies, Ongoing Trials

Conﬂicts of interests pertinent to the abstract

D. Jagadeesh

Employment or leadership position: Cleveland Clinic Taussig Cancer

Institute and Case Comprehensive Cancer Center

Consultant or advisory role: Atara Biotherapeutics, Verastem, Kyowa

Kirin

Research funding: Seagen Inc., Regeneron, MEI Pharma, Debiopharm

Group, Trillium Therapeutics, AstraZeneca, ADC Therapeutics, Rhi-

zen Pharmaceuticals

S. Knowles

Employment or leadership position: Seagen Inc., University of

Washington

Research funding: Seagen Inc.

Educational grants: Seagen Inc.

S. M. Horwitz

Employment or leadership position: Memorial Sloan Kettering Can-

cer Center

Consultant or advisory role: Celgene, Millennium, Kyowa Kirin, Sea-

gen, ADC Therapeutics, Portola, Verastem, Takeda, Astex, Kura

Oncology, Acrotech Biopharma, C4 Therapeutics, Janssen Oncology,

Trillium, Vividion, Myeloid Therapeutics, Ono

Research funding: Celgene, Seagen, Takeda, Kyowa Kirin, Aileron

Therapeutics, ADC Therapeutics, Verastem, Forty Seven, Trillium,

Daiichi Sankyo, Afﬁmed, Portola, Corvus

220 | PERIPHERAL T‐CELL LYMPHOMAS INVOLVING CENTRAL

NERVOUS SYSTEM: A REPORT FROM THE CZECH LYMPHOMA

STUDY GROUP REGISTRY

H. Mocikova

, R. Pytlik

, K. Benesova

, A. Janikova

, J. Duras

, A.

Sykorova

, K. Steinerova

, V. Prochazka

, V. Campr

, D. Belada

, J.

Dlouha

, M. Trneny

University Hospital Kralovske Vinohrady and Third Faculty of

Medicine, Charles University, Department of Haematology, Prague,

Czech Republic,

Institute of Haematology and Blood Transfusion, Cell

Therapy Department, Prague, Czech Republic,

Charles University,

General Hospital, First Department of Medicine, Department of

Hematology, Prague, Czech Republic,

University Hospital Brno,

Department of Hematology and Oncology, Brno, Czech Republic,

University Hospital and Faculty of Medicine, Department of

Hemato‐Oncology, Ostrava, Czech Republic,

University Hospital and

Faculty of Medicine, 4th Department of Internal Medicine– Hematol-

ogy, Hradec Kralove, Czech Republic,

University Hospital , Department

of Clinical Hematology, Pilsen, Czech Republic,

Faculty of Medicine

and Dentistry, Palacky University, Department of Haemato‐Oncology,

Olomouc, Czech Republic,

University Hospital Motol, Institute of Pa-

thology and Molecular Medicine, Prague, Czech Republic,

Czech

Lymphoma Study Group Registry, Data Management Ofﬁce, Prague,

Czech Republic

Introduction: We analyzed the incidence, risk factors of central

nervous system (CNS) relapse and outcome of CNS involvement in

patients with peripheral T‐cell lymphomas (PTCL) prospectively

observed in the Czech Lymphoma Study Group Registry

(NCT03199066).

Methods: Out of 1040 patients with peripheral T‐cell lymphomas

(PTCL) we identiﬁed 29 patients (2.79%) with central nervous

system (CNS) involvement: 13 patients (1.25%) had CNS disease at

initial diagnosis and 16 patients (1.54%) at relapse. Median age at

initial CNS diagnosis was 61 years and at CNS relapse 54.5 years.

Initial CNS disease concurrently with systemic lymphoma involve-

ment was documented in 11 of 13 patients and at relapse in 12 of

16 patients. The incidence of meningeal involvement was compa-

rable at initial diagnosis and in CNS relapsed patients (9 vs 11).

Most common histology with CNS disease was PTCL not otherwise

speciﬁed (10 cases at initial diagnosis and 8 cases at relapse). CNS

prophylaxis was not used in PTCL. High dose methotrexate based

treatment was administered in 44.8% of patients with CNS

disease.

Results: Median follow‐up of all patients with PTCL was 71.3

months. Median progression‐free survival (PFS) of all patients

was 32.6 months, with initial CNS disease 4.8 months and at CNS

relapse 5 months. Risk factors for CNS relapse included: involve-

ment of more than one extranodal site (p = 0.008), soft tissue

involvement (p = 0.003), testicular involvement (p = 0.046) and

presence of B symptoms (p = 0.035). Median overall survival (OS)

of all PTCL patients was 46 months, with initial CNS disease 18.2

months, at CNS relapse 11.8 months and at relapse outside of

CNS 18,9 months. CNS involvement was not associated with a

signiﬁcantly worse OS compared with relapsed/refractory patients

without CNS involvement (p = 0.072).

Conclusions: The incidence of CNS disease at initial diagnosis and at

relapse in PTCL is low and concurrent systemic involvement is found

in most of these patients. The prognosis is poor, however, the

304

SUPPLEMENT ABSTRACTS

outcome is comparable with relapsed systemic disease. Optimal

treatment is not yet deﬁned.

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

221 | CLINICAL CHARACTERISTICS AND OUTCOMES OF

ADULT LYMPHOMA‐ASSOCIATED HEMOPHAGOCYTIC

LYMPHOHISTIOCYTOSIS (HLH)

C. Y. Lee

, B. Wills Sanin

, S. A. Vardhana

, A. J. Moskowitz

Memorial Sloan Kettering Cancer Center, Medicine, New York, USA

Introduction: Lymphoma is a major cause of secondary HLH, a

life‐threatening hyperinﬂammatory syndrome due to immune dys-

regulation. This study examines the clinical and biological charac-

teristics, management, and outcomes of patients with lymphoma and

HLH.

Methods: We retrospectively reviewed 44 adult patients with

combined diagnoses of lymphoma and HLH at Memorial Sloan

Kettering Cancer Center between June 2012 and September 2020.

Overall survival (OS) was measured from the date of HLH diag-

nosis to the date of death or last follow‐up. We evaluated the

association of demographic, clinical, laboratory, and treatment

variables on survival using log‐rank tests and Cox proportional

hazards model.

Results: Of the 44 patients, 30 (68%) had T and NK‐cell lym-

phoma, 12 (27%) had B‐cell lymphoma, and 2 (5%) had Hodgkin

lymphoma. All but one patient received HLH therapy including

corticosteroids (95%), etoposide (68%), and intravenous immuno-

globulin (18%), which was initiated within 1 day of diagnosis in

84% of cases. Twenty‐ﬁve patients (57%) received lymphoma‐

directed therapy with etoposide (n = 17) or without etoposide

(n = 8). Five of the 15 patients who underwent targeted tumor‐

sequencing of 400 genes harbored a TP53 mutation and all were

refractory to frontline therapy, while 7 of 10 patients without

TP53 mutation demonstrated initial treatment response (p = 0.03).

The median OS (mOS) of the entire cohort was 1.4 months, with a

30‐day cumulative mortality incidence of 36.4%. Most deaths were

attributed to relapsed or refractory HLH (n = 25/36, 69%) and

lymphoma progression (n = 6/36, 17%). Patients with T/NK‐cell

lymphoma‐associated HLH had a mOS of 1.4 months compared to

9.2 months in B‐cell lymphomas (p = 0.09). Ten patients (23%)

were diagnosed with HLH within 60 days of their initial lymphoma

diagnosis and had an improved prognosis (mOS 12.8 vs 1.3

months, p < 0.01). Treatment with etoposide, either alone or as

part of a lymphoma‐directed regimen, was associated with signif-

icantly improved survival (HR 0.48, 95% CI 0.24‐0.96) whereas

lymphoma‐directed therapy with or without etoposide was not (HR

0.66, 95% CI 0.34‐1.29). Signiﬁcant predictors of mortality

included age ≥60 years, non‐white race, and concurrent infection

during the hospitalization.

Conclusions: In this large cohort from a single U.S. institution, there

was a wide range of lymphoma subtypes associated with HLH.

Despite increased disease recognition and prompt initiation of

standard HLH and lymphoma‐directed therapies, the prognosis re-

mains very poor. Patients treated with etoposide had improved

survival, highlighting the importance of controlling hyper-

inﬂammation during initial management. Notably, TP53 mutation was

associated with primary refractory HLH. Future studies will aim to

elucidate the pathophysiology of lymphoma‐associated HLH in order

to inform novel therapeutic approaches.

EA – previously submitted to ASCO 2021.

The research was funded by: Lymphoma Research Foundation Lym-

phoma Clinical Research Mentoring Program

Keywords: Other

No conﬂicts of interest pertinent to the abstract.

TABLE 1 Clinical characteristics

TABLE 2 Lymphoma subtypes

SUPPLEMENT ABSTRACTS

305

222 | HEPATOSPLENIC T CELL LYMPHOMA: CLINICAL

CHARACTERISTICS AND SURVIVAL

F. Baidoun

, M. Alhaj Moustafa

, H. W. Tun

, B. T. Hill

, D. Jagadeesh

Cleveland Clinic Foundation, Hospital Medicine Department, Cleveland,

USA,

Mayo Clinic‐Florida, Hematology Oncology Division, Jacksonville,

Florida, USA,

Cleveland Clinic Foundation, Department of Hematology

and Medical Oncology, Cleveland, Ohio, USA

Introduction: Hepatosplenic T cell lymphoma (HSTCL) is a rare type

of T cell lymphoma (TCL) that accounts for <1% of non‐Hodgkin

lymphomas. Outcomes in this disease is dismal due to lack of effec-

tive standard therapy. In this study, we aimed to evaluate patient and

disease factors impacting overall survival (OS).

Materials and Methods: The national cancer database (NCDB) was

queried for patients diagnosed with HSTCL between 2004 and 2017.

All patients age ≥18 years diagnosed with hepatosplenic lymphoma

(ICD‐O ‐3 histology code 9716 was used to deﬁne the diagnosis)

were included. We excluded patients with multiple primary

malignancies, no follow up or unknown vital status. Kaplan‐Meier and

multivariate Cox regression analyses were used to estimate OS and

to identify prognostic factors for survival.

Results: Of the 294 HSTCL patients included in the analysis, 200

(68%) were males, 194 (66%) Caucasian and 80 (27%) African

American. The median age at diagnosis was 46 (range 18‐88) years

and median follow‐up was 62.3 ± 7.2 (95% CI 48.3‐76.4) months.

Median overall survival for the whole cohort was 11.8 ± 1.4 (95% CI

8.94‐14.58) months. After excluding 81 patients (unknown chemo-

therapy status (n = 6), chemotherapy start time unknown (n = 61),

and treated entirely outside of the reporting facility (n = 14)), the

time to treat (TTT) from diagnosis to chemotherapy start was ≤7

days in 47 patients, within 8‐29 days in 97 patients and ≥30 days in

69 patients. Patients with longer TTT (≥30 days) had superior median

OS (24.9 months) compared to patients who received treatment

sooner (7.1 months for 8‐29 days and 8.8 months for ≤7 day group )

(P < 0.001 for both).

In univariate analysis, female gender was prognostic for OS

(median OS 23 vs 10 months, P = 0.011), but the type of treatment

FIGURE 1 Overall survival

306

SUPPLEMENT ABSTRACTS

had no impact ‐ splenectomy vs no splenectomy (median OS 11.22 vs

7.05 months, P = 0.113), hematopoietic stem cell transplantation

(HSCT) vs no HSCT (median OS 14.40 vs 11.30 months, P = 0.662)

and chemotherapy vs no chemotherapy (median OS 11.39 vs 10.02

months, P = 0.323).

Also, there was no difference in OS observed between different

treatment modalities [chemo only (143 patients), splenectomy

only (21 patients), chemo with splenectomy (51 patients), chemo

with HSCT (12 patients), splenectomy with chemo and HSCT

(10 patients)]. Compared to no treatment, only splenectomy

with chemotherapy was prognostic for OS (18.6 vs 2.9 months,

P = 0.030).

On multivariate analysis, female gender (HR 0.664 95% CI

0.462‐0.954; P = 0.027) and splenectomy (HR 0.611 95% CI 0.418‐

0.892; P = 0.011) were associated with better OS, whereas

chemotherapy and HSCT had no impact (HR 1.010 95% CI 0.634‐

1.608; P = 0. 967 and HR 0.951 95% CI 0.563‐1.607; P = 0. 852,

respectively).

Conclusion: In this large real‐world cohort based analysis of HSTCL,

female gender and treatment with splenectomy were associated with

better OS, while chemotherapy and HSCT failed to improve survival.

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

223 | SUBTYPES OF MATURE T AND NK CELL LYMPHOMAS

ACCORDING TO 2016 WHO CLASSIFICATION. PRELIMINARY

REPORT OF THE INTERNATIONAL PROSPECTIVE T‐CELL

PROJECT 2.0

M. Federico

, C. S. Chiattone

, H. M. Prince

, A. Pavlovsky

, M.

Manni

, M. Civallero

, T. Skrypets

, C. A. De Souza

, E. A. Hawkes

, L.

Fiad

, A. Lymboussakis

, C. Tomuleasa

, R. Nair

, J. Pereira

, P.

Pereyra

, C. Minoia

, I. Kryachok

, N. S. de Castro

, R. H.

Advani

, S. Luminari

University of Modena and Reggio Emilia, Surgical, Medical and Dental

Department of Morphological Sciences related to Transplant, Oncology

and Regenerative Medicine, Modena, Italy,

Santa Casa de Sao Paulo,

School of Medical Sciences, São Paulo, Brazil,

Epworth Healthcare,

East Melbourne, Richmond, Australia,

Fundaleu, Haematology, Buenos

Aires, Argentina,

Universidade de Campinas, (UNICAMP), Campinas,

Brazil,

Lymphoma and Related Diseases Registry, School of Public

Health and Preventive Medicine Monash University and Olivia Newton

John Cancer Research Institute, Austin Health, Melbourne, Australia,

Hospital Italiano La Plata, Department of Hematology and Oncology,

Buenos Aires, Argentina,

Ion Chiricuta Oncology Institute, Department

of Hematology, Cluj Napoca, Romania,

TATA Medical Center, Clinical

Haematology Oncology, Kolkata, India,

Universidade de São Paulo,

Hospital das Clínicas da Faculdade de Medicina, São Paulo, Brazil,

Hospital Nacional Dr. Prof. Alejandro Posadas, Hematology, Buenos

Aires, Argentina,

IRCCS Cancer Institute "Giovanni Paolo II",

Haematology Unit, Bari, Italy,

National Cancer Institute,

Oncohematology Department, Kiev, Ukraine,

Hospital de Cancer de

Barretos, Hematology, Barretos, São Paulo, Brazil,

Stanford Cancer

Center, Blood and Marrow Transplant Program, Stanford, California,

USA,

Azienda Unità Sanitaria Locale IRCCS, Arcispedale Santa Maria

Nuova IRCCS, Hematology Unit and, University of Modena and Reggio

Emilia, Surgical, Medical and Dental Department of Morphological

Sciences related to Transplant, Oncology and Regenerative Medicine,

Reggio Emilia, Italy

Introduction: Mature T and NK‐cell lymphomas represent a het-

erogeneous group of lymphoid disorders (29 subtypes according

to the 2016 WHO classiﬁcation) arising from mature T cells of

post‐thymic origin with different morphological characteristics,

phenotypes, and clinical presentation. Following the success of the

T Cell Project (TCP), which allowed the analysis of more than

1,500 cases of peripheral T‐Cell lymphomas (PTCLs) collected

prospectively in 18 Countries, in 2018 the TCP 2.0 was launched.

Here we report the global distribution of PTCLs, from the cases

registered so far based on the locally established histological

diagnosis.

Methods: The TCP2.0 (ClinicalTrials.gov Identiﬁer: NCT03964480) is

a prospective, international, observational study which adapts to

changes made in the new WHO classiﬁcation.

Results: Since the beginning of the study (October 2018), 648 patients

with newly diagnosed PTCL were registered by 75 active centers

across 14 countries. Of these data, 594 patients have been validated

by the centralized trial ofﬁce. Overall, PTCL‐NOS, Anaplastic large cell

lymphoma (ALCL) ALK‐negative, and Angioimmunoblastic T‐cell lym-

phoma (AITL), represent the most frequent subtypes, representing

31.3%, 18,9% and 13,5% of cases, respectively.

As reported in Table 1, PTCL‐NOS represents the most frequent

subtype worldwide, whereas Adult T‐cell leukemia/lymphoma was

more frequent in Brazil, AITL and ALCL ALK‐negative in Australia/

India, and ALCL ALK‐positive in North America and Europe. Extra-

nodal NK/T‐cell lymphoma, nasal type was relatively frequent in

Brazil and quite rare in the other Latin America Countries. Finally,

many sub‐types represent less than 5% of cases in all geographic

areas.

Conclusions: The TCP2.0 continues to recruit very well, despite the

difﬁculties linked to the COVID‐19 pandemic, and may represent a

useful resource for the prospective study of this group of rare

lymphomas.

The research was funded by: Associazione Angela Serra per la

Ricerca sul Cancro

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma, Pathology and

Classiﬁcation of Lymphomas

Conﬂicts of interests pertinent to the abstract

E. A. Hawkes

Other remuneration: Takeda, Roche

SUPPLEMENT ABSTRACTS

307

224 | CIRCULATING TUMOR DNA BY HIGH‐THROUGHPUT

SEQUENCING OF T CELL RECEPTOR MONITORED TREATMENT

RESPONSE AND PREDICTED TREATMENT FAILURE IN T CELL

LYMPHOMAS

W. Wang

, W. Zhang

, Y. Zhang

, Y. Gan

, L. Qian

, D. Zhou

peking union medical college hospital, hematology, Beijing,

China

Introduction: Next‐generation sequencing (NGS)‐based circulating

tumor DNA (ctDNA) detection is a promising monitoring tool

for lymphoid malignancies. Studies for T cell lymphoma are limited.

Objective: To explored whether next‐generation sequencing (NGS)‐

based circulating tumor DNA (ctDNA) detection is applicable to T cell

lymphoma and assessed its performance in clinical settings.

Methods: We ﬁrst identiﬁed tumor clones, identiﬁed as any CDR3

sequences that accounted more than 5%, by TCR sequencing in

pathological specimens. Then use these sequences to capture circu-

lating tumor DNA in plamsa. Any non‐zero result in the plasma was

considered positive molecular disease. Results of ctDNA were

compared with PET/CT or the clinical outcome.

Results: 30 tumor and 74 blood samples were analyzed in our study.

Malignant clone was identiﬁed in 23 of the 30 (76.7%) tumor samples

through high‐throughput sequencing (HTS) combined with PCR. We

detected the same tumor clone in plasma in 18 out of the 23 (78.3%)

patients. Circulating tumor DNA fraction correlated with lactate

dehydrogenase (LDH) (r = 0.52, p = 0.017), high level of ctDNA

predicted treatment failure (p = 0.0003) and there was a trend pa-

tients with high ctDNA burden would have poorer PFS. Furthermore,

ctDNA changed in concordance with clinical outcome and was more

sensitive than PET/CT. Also, recurrence of ctDNA was an important

clue for relapse.

Conclusion: In conclusion, our study indicated that ctDNA moni-

toring was suitable for T cell lymphoma. High level of pretreat-

ment ctDNA was a poor prognosis factor and changes of ctDNA

correlated well with clinical courses and was sensitive to ﬁnd early

relapse.

EA – previously submitted to EBMT, AACR, ASCO and EHA 2021.

The research was funded by: National Natural Science Foundation of

China (NSFC) (No. 81970188) CAMS Innovation Fund for Medical

Sciences(CIFMS) 2016‐12M‐1‐001 Innovation project ‐ major

collaborative innovation 2019‐I2M‐2‐009 Beijing Municipal Natural

Science Foundation (BNSF) (No.7202154)

Keywords: Liquid biopsy

No conﬂicts of interest pertinent to the abstract.

308

SUPPLEMENT ABSTRACTS

225 | IMPACT OF DUSP22 REARRANGEMENT ON THE

PROGNOSIS OF SYSTEMIC ALK‐NEGATIVE ANAPLASTIC LARGE

CELL LYMPHOMA: A LYSA AND TENOMIC STUDY

D. Sibon

, B. Bisig

, C. Bonnet

, E. Bachy

, D. Cavalieri

, V. Fataccioli

F. Drieux

, J. Bruneau

, F. Lemonnier

, C. Bossard

, K.

Bouabdallah

, M. Parrens

, G. Damaj

, O. Tournilhac

, J. P. Jais

P. Gaulard

, L. de Leval

Necker University Hospital, Hematology, Paris, France,

Lausanne

University Hospital, Pathology, Lausanne, Switzerland,

Liège University

Hospital, Clinical Hematology Unit, Liège, Belgium,

Lyon‐Sud University

Hospital, Hematology, Pierre‐Bénite, France,

Clermont‐Ferrand University

SUPPLEMENT ABSTRACTS

309

Hospital, Hematology, Clermont‐Ferrand, France,

Mondor University

Hospital, Pathology, Créteil, France,

Henri Becquerel Cancer Center, Pa-

thology, Rouen, France,

Necker University Hospital, Pathology, Paris,

France,

Mondor University Hospital, Hematology, Créteil, France,

Nantes

University Hospital, Pathology, Nantes, France,

Haut‐Lévêque University

Hospital, Hematology, Bordeaux, France,

Haut‐Lévêque University Hos-

pital, Pathology, Bordeaux, France,

Caen University Hospital, Hematolo-

gy, Caen, France,

Necker University Hospital, Statistics, Paris, France

Introduction: ALK‐negative anaplastic large cell lymphoma (ALCL) is

a CD30+ T‐cell neoplasm which can sometimes harbour a DUSP22

rearrangement (DUSP22‐R) on 6p25.3. In the ﬁrst clinical report, the

5‐year OS of 22 patients with DUSP22‐R was 90% (Parrilla Castellar

et al, Blood 2014). However, in a later work from the British

Columbia Cancer Lymphoid Cancer database, the 5‐year OS of 12

patients with DUSP22‐R was 40% (Hapgood et al, BJH 2019). Thus,

the prognostic impact of DUSP22‐R is currently unclear.

Methods: Systemic ALK‐negative ALCL cases were collected through

the LYSA pathology institute and Tenomic, a transnational research

consortium on T‐cell lymphomas involving several centers in France,

Belgium and Switzerland. For the purpose of the present study,

two expert hematopathologists (L.d.L. and P.G.) reviewed cases coded

as ALK‐negative ALCL or CD30+ PTCL‐NOS and extended the

phenotypic analysis to reclassify them according to the WHO clas-

siﬁcation. FISH studies for DUSP22 and TP63 rearrangements were

carried out and analysed centrally. Clinical features and outcomes are

described.

Results: Among the 100 retrieved ALK‐negative ALCL cases, 45

harboured a DUSP22‐R. As shown in the Table below, bone

involvement was the only signiﬁcant parameter, more frequent in

DUSP22‐R cases (p = 0.01). Median follow‐up of living patients was

4.3 years. 5‐year PFS was 32% for the 100 patients, including 46%

and 21% for the DUSP22‐R and non‐R patients, respectively (p <

0.01). 5‐year OS was 50% for the 100 patients, including 57% and

45% for the DUSP22‐R and non‐R patients, respectively (p = 0.32).

Conclusion: In our cohort, the largest to date, DUSP22‐R had no

statistically signiﬁcant impact on OS.

Keywords: Diagnostic and Prognostic Biomarkers Aggressive T‐cell

non‐Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

226 | SUBCUTANEOUS PANNICULITIS‐LIKE T‐CELL

LYMPHOMA: MOLECULAR AND MUTATIONAL

CHARACTERIZATION COMPARED WITH LUPUS PANNICULITIS

AND HISTOPATHOLOGIC OVERLAPPING CASES

S. Machan

, M. Rodriguez

, R. Manso

, J. Borregon

, C. Chamizo

, R.

Alonso‐Alonso

, S. Pérez Buira

, J. L. Rodríguez‐Peralto

, L. Cerroni

L. Cereceda

, R. Córdoba

, M. Án. Piris

, L. Requena

, S. María

Rodríguez‐Pinilla

Fundación Jiménez Díaz‐Universidad Autónoma de Madrid,

Dermatology, Madrid, Spain,

Fundación Jiménez Díaz, Pathology,

Madrid, Spain,

Hospital Universitario 12 de Octubre, Pathology, Madrid,

Spain,

Medical University of Graz, Dermatology, Graz, Austria,

Fundación Jiménez Díaz, Hematology, Madrid, Spain

Clinical features at

diagnosis

DUSP22‐

rearranged

cases

DUSP22‐non

rearranged

cases p

N 45 55

Era 2004‐2019 2001‐2019

Median age, y (range) 60 (40‐86) 62 (39‐85) NS

Male 35/45 38/55 NS

PS ≥ 2 14/44 21/54 NS

Stage

1 4/45 3/55 NS

2 8/45 11/55

3 4/45 16/55

4 29/45 25/55

Extranodal site (any)

Bone 14/45 5/54 0.01

Liver 9/45 7/54 NS

Spleen 8/45 6/54 NS

Bone marrow 6/45 7/54 NS

Lung 7/45 4/54 NS

Skin 7/45 4/54 NS

Soft tissue 2/45 9/54 NS

GI tract 3/45 4/54 NS

Pleural effusion/ascites 1/45 0/54 NS

Blood 0/45 1/54 NS

Extranodal site >1 14/45 14/55 NS

Elevated LDH 28/44 29/54 NS

B2‐microglobulin ≥ 3

mg/L

7/21 16/34 NS

IPI

0‐1 14/44 12/54 NS

2 8/44 15/54

3 10/44 15/54

4‐5 12/44 12/54

Primary therapy

CHOP/CHOP‐like 44/45 51/55 NS

Other regimen 0/45 3/55

Palliative care 1/45 1/55

Consolidative AutoSCT 7/45 5/55 NS

Consolidative AutoSCT 3/45 3/55 NS

310

SUPPLEMENT ABSTRACTS

Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) is a rare

cytotoxic primary cutaneous lymphoma whose histopathologic dif-

ferential diagnosis with lupus erythematosus panniculitis (LEP) can

be challenging, and overlapping cases have been described. In this

study we investigate whether gene expression proﬁling using a

customized NanoString platform may identify markers that can be

used to improve our understanding of the disease and to make a

more precise differential diagnosis. Twenty‐two cases of SPTCL, LEP

and overlapping cases were analyzed using a customized NanoString

platform that includes 208 genes related to T‐cell differentiation,

stromal signatures, oncogenes and tumor suppressor genes. Unsu-

pervised analysis of the gene expression of the samples identiﬁed

three clusters of samples that differentiated SPTCL from LEP sam-

ples. Most overlapping cases (4/5) were clustered with LEP cases, and

only one case was grouped with the SPTCL cases. We identiﬁed 60

and 30 genes that were respectively upregulated and downregulated

in SPTCL compared with LEP. Differentially expressed genes were

observed when comparing overlapping with LEP cases. Gene set

enrichment analysis recognized gene sets deﬁning each group. We

identiﬁed mutations in epigenetic modiﬁcatory genes ARID1A, EZH2,

TET2, DNMT3A, and NCOR1; the tumor suppressor gene TP53, and

PLCG1 gene in four out of the six SPTCL samples analyzed. Only

one case showed HAVCR2 mutation. In conclusion, SPTCL

and LEP have distinctive molecular proﬁles. The molecular back-

ground of overlapping cases more closely resembles LEP than it does

SPTCL.

The research was funded by: Instituto de Salud Carlos III, from the

Ministry of Science and Innovation of Spain, PI17/2172.

Keywords: Diagnostic and Prognostic Biomarkers, Cutaneous non‐

Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

227 | CHARACTERIZATION OF THE ONCOGENIC PHENOTYPE

IN EXTRANODAL NATURAL KILLER/T‐CELL LYMPHOMA, NASAL

TYPE THROUGH GENE EXPRESSION PROFILE. SPANISH

LYMPHOMA GROUP GELTAMO

E. González‐Barca

, L. Gato

, A. Esteve

, R. Sanz‐Pamplona

, L.

Tomás

, M. Rodriguez

, A. Martín García‐Sancho

, R. Córdoba

, A.

Monter

, M. Bastos

, J. M. Bergua Burgues

, M. J. Sayas

, M. C.

Viguria Alegria

, J. J. Sánchez Blanco

, M. Roig

, H. D. Luzardo

Henriquez

, R. Oña

, E. Cabezudo

, M. S. Infante

, J. A. Quei-

zan

, O. Blanco Nuñez

, A. Mozos

, F. Climent

, M. A. Piris

Institut Català d’Oncologia, Hospital Duran i Reynals, Institut

d’Investigació Biomèdica de Bellvitge (IDIBELL), Universitat de

Barcelona, Hematology, L’Hospitalet de Llobregat, Barcelona, Spain,

Fundación Jiménez Díaz, CIBERONC, Pathology, Madrid, Spain,

Insititut Català d'Oncologia, Unit of Biomarkers and Susceptibility,

Oncology Data Analytics Program (ODAP); Medical Oncology

Department, B‐ARGO Badalona, Badalona, Barcelona, Spain,

Catalan

Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical

Research Institute (IDIBELL) and CIBERESP, Unit of Biomarkers and

Susceptibility, Oncology Data Analytics Program (ODAP), L'Hospitalet

de Llobregat, Barcelona, Spain,

Hospital Universitario de Salamanca,

IBSAL, Hematology, Salamanca, Spain,

Fundación Jimenez Díaz, He-

matology, Madrid, Spain,

Hospital de la Santa Creu i Sant Pau, He-

matology, Barcelona, Spain,

Gregorio Marañón General University

Hospital (HGUGM), Hematology, Madrid, Spain,

Hospital San Pedro de

Alcántara, Hematology, Cáceres, Spain,

Hospital Universitario Dr

Peset, Hematology, Valencia, Spain,

Complejo Hospitalario de Nav-

arra, Hematology, Pamplona, Spain,

Hospital Morales Messeguer,

Hematology, Murcia, Spain,

Hospital La Fe, Hematology, Valencia,

Spain,

Hospital Dr Negrín, Hematology, Las Palmas de Gran Canaria,

Spain,

MD Anderson Cancer Center, Hematology, Madrid, Spain,

Insititut Català d'Oncologia, Hospital Moises Broggi, Hematology, San

Juan Despí, Barcelona, Spain,

Hospital Infanta Leonor, Hematology,

Madrid, Spain,

Hospital General de Segovia, Hematology, Segovia,

Spain,

Hospital Universitario de Salamanca, IBSAL, Pathology, Sala-

manca, Spain,

Hospital de la Santa Creu i Sant Pau, Pathology,

Barcelona, Spain,

Hospital Universitario de Bellvitge, Institut

d'Investigaciò Biomédica de Bellvitge IDIBELL, Pathology, Hospitalet de

LLobregat, Barcelona, Spain,

Fundación Jiménez Díaz, Pathology,

Madrid, Spain

TABLE: Clinical characteristics of the 24 patients with ENKTL‐NT at

diagnose

SUPPLEMENT ABSTRACTS

311

Introduction: Extranodal natural killer (NK)/T‐cell lymphoma,

nasal type (ENKTL‐NT) is a rare and aggressive disease associated

with Epstein‐Barr virus (EBV) infection. It is much more common

in Asia and Latin America, and data from European cases are

very limited. Oncogenic alterations have not been fully described

due to its rarity and the difﬁculties inherent to a tumor with

high necrosis and minimum‐size biopsies. Treatment for ENKTL‐NT

lymphoma is mainly based on cytotoxic therapy, with very little

contribution of targeted therapy. The aim of this study is to

characterize the oncogenic phenotype in ENKTL‐NT lymphoma,

through the gene expression proﬁle (GEP) study using a dedicated

NanoString CHIP in a series of patients diagnosed of ENKTL‐NT.

Patients and Methods: Eighty‐nine patients with ENKTL‐NT diag-

nosed from 2000 to 2017 were identiﬁed in 24 academic centers in

Spain. After histological revision and quality control, a NanoString

gene proﬁle could be successfully performed in 24 cases. Normalized

count data were log2 transformed and agglomerative hierarchical

clustering of gene expression were performed. The Euclidean dis-

tance was considered.

Results: Clinical characteristics at presentation of the 24 patients did

not differ from the global series. In summary, median age was 51

years, male 58%, Caucasian 58%, extranasal ENKTL‐NT 46%. OS at 5

y was 37% (95%CI 27‐50). ENKTL‐NT cases exhibited a cytotoxic

signature including the genes GZMA, GZMB, NKG7 and PRF1.

Additionally they showed a homogeneous expression of an EBV

signature including 4 genes expressed in both lytic and latent phases.

Tumor signatures included a strong expression of immune regulator

genes as B2M and HLA‐II and a co‐regulated gene set with AKT,

PI3KCA, IKBIB, MTOR and TGFB, revealing the increased expression

of a targetable gene pathway that associates PI3K/MTOR/AKT with

NFKB and TGFB. A proliferation signature was also found, with the

expression of Ki67, E2F1, PCNA and CDK2. The analysis included the

expression of genes for targeted therapy and revealed a high

expression of both CD274 (PDL1) and PDCD1LG2 (PDL2), a variable

expression of TNFRSF8 (CD30) and intense expression of CXCR4

and PIM1.

Conclusions: ENKTL‐NT cells show a distinct signature that includes

cytotoxic genes, EBV‐expressed genes and immune regulator genes.

Data obtained in this analysis could support the introduction of

therapy targeting PDL1, PDL2 and PD1, together with anti‐CD30

therapy. Moreover, new targets have been identiﬁed, and blocking

antibodies anti‐CXCR4 or kinase inhibitors anti PIM1, used in clinical

trials in other indications, could also be tested in patients with

ENKTL‐NT.

Keywords: Aggressive T‐cell non‐Hodgkin lymphoma

No conﬂicts of interest pertinent to the abstract.

228 | PERIPHERAL T‐CELL LYMPHOMA: MOLECULAR

PROFILING DISTINGUISHES SUBCLASSES, RECOGNIZES THE

TUMOR ARCHITECTURE AND IDENTIFIES PROGNOSTIC

MARKERS

M. Rodríguez

, L. Tomás‐Roca

, R. Alonso‐Alonso

, R. Manso‐

Alonso

, L. Cereceda

, J. Borregón

, T. Villaescusa

, Raúl Córdoba

M. Sánchez‐Beato

, I. Fernández‐Miranda

, I. Betancor

, C. Bárcena

J. F. García

, M. Mollejo

, Món. García‐Cosio

, P. Martin‐Acosta

, F.

Climent

, D. Caballero

, R. Mondéjar

, L. Kessler

, C. Scholz

, A.

Gualberto

, S. M. Rodríguez‐Pinilla

, M. Án. Piris

Instituto de Investigación Sanitaria‐Fundación Jiménez Díaz University

Hospital. CIBERONC. Madrid, Spain, Pathology Department, Madrid,

Spain,

Pathology Department, Instituto de Investigación Sanitaria‐

FIGURE:

Clustering genes with normalized counts of the 24 patients

with ENKTL‐NT

312

SUPPLEMENT ABSTRACTS

Fundación Jiménez Díaz University Hospital, Pathology Department,

Madrid, Spain,

Fundación Jiménez Díaz University Hospital, Health

Research Institute IIS‐FJD, Madrid, Spain, Department of Hematology,

Madrid, Spain,

Fundación Jiménez Díaz University Hospital, Health

Research Institute IIS‐FJD, CIBERONC, Madrid, Spain., Department of

Hematology, Madrid, Spain,

Instituto de Investigación Sanitaria Puerta

de Hierro‐Segovia de Arana, CIBERONC, Madrid, Spain, Lymphoma

Research Group, Medical Oncology Department, Madrid, Spain,

Instituto

de Investigación Sanitaria Puerta de Hierro‐Segovia de Arana, Madrid,

Spain, Lymphoma Research Group, Medical Oncology Department,

Madrid, Spain,

Hospital Universitario 12 de Octubre, Madrid, Spain,

Pathology Department, Madrid, Spain,

Hospital MD Anderson Cancer

Center, CIBERONC, Madrid, Spain, Pathology Department, Madrid, Spain,

Hospital Virgen de la Salud, CIBERONC, Toledo, Spain, Pathology

Department, Toledo, Spain,

Hospital Universitario Ramón y Cajal,

CIBERONC, Madrid, Spain, Pathology Department, Madrid, Spain,

Hospital Universitario Puerta de Hierro‐Segovia de Arana, CIBERONC,

Madrid, Spain, Pathology Department, Madrid, Spain,

Hospital Uni-

versitari de Bellvitge, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain,

Pathology Department, Barcelona, Spain,

Hospitalario Universitario de

Salamanca (HUS/IBSAL), Salamanca, Spain, Haematology Department,

Salamanca, Spain,

Hospital Universitario Virgen del Rocío, CIBERONC,

Sevilla, Spain, Laboratory, Sevilla, Spain,

Kura Oncology Inc., Kura

Oncology Inc., San Diego, California, USA

Introduction: Peripheral T‐cell Lymphomas (PTCLs) are aggressive

tumours with unfavourable prognosis, with around 30% overall sur-

vival (OS) after 5 years. Histological and molecular studies have

revealed a striking degree of heterogeneity, with three major PTCL

subtypes deﬁned. Consistent diagnosis and prognostication are still

difﬁcult to achieve, because of the difﬁculty of reproducing results,

and the dearth of clinically applicable prognostic biological markers.

Methods: We have analyzed a series of 105 PTCL cases (66 angioim-

munoblastic T‐cell lymphoma, AITL; 21 PTCL‐not otherwise speciﬁed,

PTCL‐NOS; and 18 PTCL‐with T follicular helper phenotype, PTCL‐

TFH) patients using a customized NanoString platform that includes

208 genes associated with T‐cell differentiation, oncogenes and tumor

suppressor genes, deregulated pathways and stromal cell sub-

populations. Speciﬁcally, the platform includes genes expressed by the

multiple cell types present in PTCL specimens, together with normal T‐

cell populations. These are used to try and enable the deconvolution of

the T‐cell lymphoma microenvironment, and thereby develop an in-

tegrated perspective on the cell composition of PTCL tumor

specimens.

Results: A comparative analysis of the various histological types of

PTCL (AITL, PTCL‐NOS and PTCL‐TFH) showed speciﬁc sets of genes

to be associated with each of the diagnoses, including TFH markers,

cytotoxic markers and genes whose expression was a surrogate for

speciﬁc cellular subpopulations, including follicular dendritic cells,

mast cells and genes belonging to speciﬁc cell‐survival pathways (NF‐

κB). Unsupervised analysis of the expression of the genes here

studied revealed clusters of co‐regulated genes that identiﬁed the

main cell components of the tumor. The analysis did not reveal any

differences in survival probability associated with the histological

sub‐classiﬁcation, but did identify speciﬁc genes and gene sets whose

expression was associated with changes in survival probability for

each of the PTCL subtypes, independently of the clinical variables

included in the International Prognostic Index (IPI). These included a

B‐cell gene set in cases of AITL, the expression of proliferation

markers in PTCL‐NOS, and the expression of cytotoxic markers in

cases with a diagnosis of PTCL‐TFH. For each PTCL lymphoma type, a

multivariate analysis identiﬁed genes that allow the series of cases to

be stratiﬁed into different risk groups. This was validated for AITL in

an independent series of 54 additional cases.

Conclusions: In summary, our study supports the current division of

PTCL into these three categories (AITL, PTCL‐NOS and PTCL‐TFH),

identiﬁes gene sets potentially useful for this classiﬁcation and rec-

ognizes the expression of B‐cell genes as an IPI‐independent prog-

nostic factor for AITL subtype.

EA – previously submitted to regional or national meetings (up to

1000 attendees).

The research was funded by: The research was supported by grants

from Instituto de Salud Carlos III, from Ministerio de Economía,

Industria y Competitividad, Asociación Española Contra el Cáncer

(AECC), Comunidad Autónoma de Madrid and Centre for Biomedical

Network Research on Cancer (CIBERONC): SAF2013‐47416‐R,

CIBERONC‐ISCIII (CB16/12/00291), ISCIII‐MINECO‐AES‐FEDER

(Plan Estatal I + D + I 2013‐2016), ISCIII‐MINECO AES‐FEDER

(Plan Estatal I + D + I 2017‐2020), AECC PROYE18054PIRI, CAM

B2017/BMD‐3778, PIC97/2017_FJD, PIE15/0081, PI17/00272,

PIE16/01294, GILEAD (GL18/00019) and PIC 041‐19. L. Tomas‐

Roca was funded by Marie Skłodowska‐Curie Individual Fellowship

(No 882597).

Keywords: Genomics, Epigenomics, and Other ‐Omics, Diagnostic and

Prognostic Biomarkers, Aggressive T‐cell non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

M. Án. Piris

Consultant or advisory role: Millenium/Takeda, Celgene, Gilead,

Jansen, NanoString, Kyowa Kirin

Research funding: Millenium/Takeda, Gilead, Kura

229 | MUTATIONAL ANALYSIS OF THE DIFFERENT NODAL

PERIPHERAL T‐CELL LYMPHOMA SUBCLASSES

L. Tomas‐Roca

, M. Rodriguez

, R. Alonso‐Alonso

, L. Cereceda

, S.

M. Rodriguez‐Pinilla

, J. Borregón

, R. Manso

, T. Villaescusa

, R.

Córdoba

, M. Sánchez‐Beato

, I. Fernández‐Miranda

, C. Barcena

, J.

F García

, M. Mollejo

, M. García‐Cosio

, P. Martin‐Acosta

, F.

Climent

, D. Caballero

, M. A. Piris

Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Pathology

Department, Madrid, Spain,

Instituto de Investigación Sanitaria

Fundación Jiménez Díaz, Centro de Investigación Biomédica en Red de

Cáncer (CIBERONC), Pathology Department, Madrid, Spain,

Hospital

SUPPLEMENT ABSTRACTS

313

Universitario Fundación Jiménez Díaz, Haematology Department, Madrid,

Spain,

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),

Hospital Universitario Fundación Jiménez Díaz, Haematology

Department, Madrid, Spain,

Centro de Investigación Biomédica en Red de

Cáncer (CIBERONC), Instituto de Investigación Sanitaria Puerta de Hierro‐

Segovia de Arana, Medical Oncology Department, Madrid, Spain,

Lym-

phoma Research Group, Instituto de Investigación Sanitaria Puerta de

Hierro‐Segovia de Arana, Medical Oncology Department, Madrid, Spain,

Hospital Universitario 12 de Octubre, Pathology Department, Madrid,

Spain,

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),

Hospital MD Anderson Cancer Center, Pathology Department, Madrid,

Spain,

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),

Hospital Virgen de la Salud, Pathology Department, Madrid, Spain,

Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),

Hospital Universitario Ramón y Cajal, Madrid, Pathology Department,

Madrid, Spain,

Centro de Investigación Biomédica en Red de Cáncer

(CIBERONC), Hospital Universitario Puerta de Hierro‐Segovia de Arana,

Pathology Department, Madrid, Spain,

Hospital Universitari de Bellvitge,

IDIBELL, L’Hospitalet de Llobregat, Pathology Department, Barcelona,

Spain,

Hospitalario Universitario de Salamanca (HUS/IBSAL), Pathology

Department, Madrid, Spain,

Instituto de Investigación Sanitaria Fun-

dación Jiménez Díaz, Centro de Investigación Biomédica en Red de Cáncer

(CIBERONC), Pathology Department, Madrid, Spain

Introduction: Nodal peripheral T‐cell lymphoma (PTCL) subclassiﬁ-

cation (Angioimmunoblastic TCL, PTCL‐with T Follicular Helper

phenotype and PTCL‐NOS) and therapeutic targeting is still contro-

versial. Overall survival (OS) is only around 30% after 5 years.

Methods: We performed targeted next‐generation sequencing of 61

selected genes in 76 PTCL patients. Among the 76cases, 44 were

classiﬁed as AITL, 18 as PTCL‐TFH and 14 as PTCL‐NOS.

Results: Our analysis revealed a wide variety of genetic variants that

possibly drive the development of AITL, PTCL‐TFH and/or PTCL‐NOS.

We identiﬁed an average of 4 variants per patient, mainly clustered in

genes regulating chromatin conformation (TET2, DNMT3A) and T‐cell

differentiation (RHOA, MTOR, IDH2, VAV1 and NOTCH1). More

frequently mutated genes were TET2 (76,31%) and DNMT3A (27,63%).

Multiple mutations were found in TET2, VAV1, RHOA, NOTCH1, MTOR,

JAK1, ZEB1, ATM, DNMT3A and ARID1B.

Main difference among the three Nodal PTCL classes was

the higher frequency of RHOA

G17V

mutations (p < 0.0001), pre-

sent approximately 2 times more frequently in AITL cases (34,09%)

than in PTCL‐TFH (16,66%), and they were not detected in PTCL‐NOS.

All three Nodal PTCL subtypes share ﬁnding suggesting Clonal

Hematopoiesis (CH) in TET2 and DNMT3A genes. Cases with higher

variant allele frequencies (VAF)s in TET2 and DNMT3A genes vs.

other mutated genes were attributed to CH. In our study we found

this phenomenon to take place in all Nodal PTCL subtypes (AITL:

31,8%; PTCL‐TFH: 50%; PTCL‐NOS: 35,71%). A correlation was not

found between speciﬁc mutations, mutational index, mutations

attributed to CH and clinical outcome.

Conclusions: There is a common molecular basis for the three Nodal

PTCL with very frequent mutations in genes regulating chromatin

conformation associated with mutations in genes governing T‐cell

differentiation. RHOA G17V mutations were highly signiﬁcant

enriched in AITL. Findings suggesting Clonal Hematopoiesis were

found in the three types of nodal PTCL.

The research was funded by: The research was supported by grants

from Instituto de Salud Carlos III, from Ministerio de Economía,

Industria y Competitividad, Asociación Española Contra el Cáncer

(AECC), Comunidad Autónoma de Madrid and Centre for Biomedical

Network Research on Cancer (CIBERONC): SAF2013‐47416‐R,

CIBERONC‐ISCIII (CB16/12/00291), ISCIII‐MINECO‐AES‐FEDER

(Plan Estatal I + D + I 2013‐2016), AECC PROYE18054PIRI, CAM

B2017/BMD‐3778, PIC97/2017_FJD, PIE15/0081, PIE16/01294 and

PI19/00715. L.Tomas‐Roca was funded by Marie Skłodowska‐Curie

Individual Fellowship (No 882597).

Keywords: Diagnostic and Prognostic Biomarkers, Pathology and

Classiﬁcation of Lymphomas

Conﬂicts of interests pertinent to the abstract

M. A. Piris

Consultant or advisory role: Millenium/Takeda, Celgene, Gilead,

Jansen

Research funding: Millenium/Takeda, Gilead, Kura

Other remuneration: Lectures fees Millenium/Takeda, Jansen,

Nanostring, Kyowa Kirin

NEW DRUGS

230 | WITHDRAWN

231 | PRMT5 INHIBITION RESTARTS A PRO‐APOPTOTIC

PROGRAM AND CREATES VULNERABILITY TO COMBINATION

TREATMENT WITH BCL‐2 INHIBITOR VENETOCLAX IN MANTLE

CELL LYMPHOMA

F. Brown

, I. Hwang

, S. Sloan

, C. Hinterschied

, J. Helmig‐Mason

M. Long

, Y. Youssef

, W. Chan

, A. Prouty

, J. Chung

, Y. Zhang

, S.

Chen‐Kiang

, M. DiLiberto

, O. Elemento

, L. Sehgal

, L. Alinari

, P.

Scherle

, K. Vaddi

, R. Lapalombella

, J. Paik

, R. A. Baiocchi

The Ohio State University, Department of Hematology, Columbus, USA,

Weil Cornell Medicine, Department of Pathology and Laboratory

Medicine, New York, USA,

Prelude Therapeutics, R&D, Wilmington,

Delaware, USA,

Weil Cornell Medicine, Department of Physiology &

Biophysics, New York, New York, USA

Mantle cell lymphoma (MCL) is an incurable B cell malignancy,

comprising 5% of non‐Hodgkin lymphomas diagnosed annually. MCL

is associated with a poor prognosis due to emergence of resistance to

immuno‐chemotherapy and targeted agents. The average overall

survival of patients with MCL is 4‐6 years and for the majority of

patients who progress on targeted agents, survival remains at a

314

SUPPLEMENT ABSTRACTS

dismal 3‐8 months. There is a major unmet need to identify new

therapeutic approaches that are well tolerated to improve treatment

outcomes and quality of life.

The type II protein arginine methyltransferase enzyme, PRMT5 is

overexpressed and promotes growth and survival of MCL. Inhibition

of PRMT5 with a novel, SAM‐competitive class of inhibitors drives

anti‐tumor activity in MCL cell lines and patient derived xenograft

models derived from patients with relapse or refractory disease.

Selective inhibition of PRMT5 in these models and MCL cell lines

leads to disruption of constitutive PI3K/AKT signaling, dephosphor-

ylation and nuclear translocation of FOXO1, and enhanced recruit-

ment of this tumor suppressor protein to target genes. By performing

chromatin immunoprecipitation‐seq analysis, we identiﬁed over 800

newly emerged FOXO1‐bound genomic loci, among which pro‐

apoptotic BH3 family members including multiple pro‐apoptotic

BCL2 family proteins. BAX was identiﬁed as the most common

direct target of FOXO1‐transriptional activity which led us to hy-

pothesize that PRMT5 inhibition could potentially drive a therapeutic

vulnerability to the BCL‐2 inhibitor venetoclax.

Single agent and combination treatment with venetoclax and

PRT382 was performed in nine MCL lines and IC50 and synergy

scores showed signiﬁcant levels of synergy in the majority of MCL

lines tested. CCMCL1, a BCL‐2 negative MCL line, and Maver1,

which is highly resistant to PRMT5i, were the only cell lines to not

show synergy. The cell line with the highest levels of synergy, Z‐138,

expressed high levels of BCL‐2 and is ibrutinib resistant. Overall,

there was a strong positive correlation between BCL‐2 expression

and synergy score (r = ‐0.8956, p = 0.0064).

In vivo evaluation in two preclinical MCL models showed thera-

peutic synergy with combination venetoclax/PRT382 treatment.

Mice were treated with sub‐therapeutic doses of venetoclax and/or

PRT382 and disease burden was assessed weekly via ﬂow cytometry.

Combination treatment with well‐tolerated doses of venetoclax and

PRMT5 inhibitors in the MCL in vivo models showed synergistic anti‐

tumor activity. Both PDX models showed an extension of life with

combination treatment (P < 0.001) and delayed disease progression

(P < 0.05). This preclinical data provides mechanistic rationale while

demonstrating therapeutic synergy in this preclinical study and

justiﬁes further consideration of this combination strategy target-

ing PRMT5 and BCL2 in MCL in the clinical setting.

EA – previously submitted to EHA 2021.

The research was funded by: The College of Medicine at The Ohio

State University, USA; The NIH, USA; Prelude Therapeutics, USA;

Keywords: Genomics, Epigenomics, and Other ‐Omics, Molecular

Targeted Therapies, Combination Therapies

Conﬂicts of interests pertinent to the abstract

Y. Zhang

Employment or leadership position: Prelude Therapeutics

P. Scherle

Employment or leadership position: Prelude Therapeutics

K. Vaddi

Employment or leadership position: Prelude Therapeutics

R. A. Baiocchi

Consultant or advisory role: Prelude Therapeutics

Research funding: Prelude Therapeutics

232 | CC‐99282 IS A NOVEL CEREBLON E3 LIGASE

MODULATOR (CELMOD) AGENT WITH POTENT AND BROAD

ANTITUMOR ACTIVITY IN PRECLINICAL MODELS OF DIFFUSE

LARGE B‐CELL LYMPHOMA (DLBCL)

A. Lopez‐Girona

, L. Groocock

, Z. Mo

, R. K. Narla

, P. Janardhanan

S. Wood

, D. Mendy

, L. Barnes

, S. Peng

, D. Jankeel

, C. Fontanillo

S. Carrancio

, J. Hansen

Bristol Myers Squibb, Oncogenesis Therapeutic Research Center,

Princeton, New Jersey, USA,

Bristol Myers Squibb, Informatics and

Predictive Sciences, Princeton, New Jersey, USA,

Bristol Myers Squibb,

Small Molecule Drug Discovery, Princeton, New Jersey, USA

Introduction: CC‐99282 is an Ikaros‐ and Aiolos‐targeting oral

CELMoD agent in development for the treatment of relapsed/re-

fractory non‐Hodgkin lymphomas (R/R NHL). While patients with R/

R NHL tend to have poor prognoses, agents mediating Ikaros/Aiolos

degradation, such as lenalidomide (LEN) and avadomide (AVA), have

shown promise in the R/R NHL setting.

Methods: The effects of CC‐99282 were studied in lymphoma and

nontumorigenic human cell lines, primary cells, and lymphoma

xenograft models. Shotgun proteomics, immunoblotting, enzyme

fragment complementation assays, and ﬂow cytometry studies

assessed substrate degradation selectivity of CC‐99282. CRISPR/

Cas9 gene editing was performed in lymphoma cell lines and a T‐cell

restimulation assay evaluated immune‐stimulatory effects.

Results: CC‐99282 demonstrated potent autonomous cell killing and

apoptosis in DLBCL cells, independent of the origin subtype, pres-

ence of high‐risk chromosomal translocations, or acquired resistance

to doxorubicin. Of 23 cell lines tested, 20 showed sensitivity to CC‐

99282 with IC

of 1–500 nM; similar low IC

values were achieved

only in 3 cell lines treated with AVA and none with LEN. No general

cytotoxicity was observed in nontumorigenic cells in culture treated

with ≤10 µM of CC‐99282. While genetic knockout of either IKZF1/

Ikaros or IKZF3/Aiolos sensitized DLBCL cells, the expression of

degradation‐resistant mutants of Ikaros/Aiolos protected them from

the antiproliferative effects of CC‐99282. The deep and sustained

degradation of Ikaros/Aiolos in DLBCL cells treated with CC‐99282

correlated with: the induction of interferon (IFN)‐inducible genes

(IRF7, IFIT3, and DDX58); a reduction of the highly critical oncogenic

factors c‐Myc and IRF4; and the induction of cleaved caspases and

PARP.

Several DLBCL xenograft models treated with CC‐99282 (1–30

mg/kg) at different dosing schedules showed signiﬁcant (P < 0.0001)

SUPPLEMENT ABSTRACTS

315

tumor regression and tumor‐free status (Figure). The strong anti-

tumor activity was accompanied with robust distribution of CC‐

99282 across multiple tissues, including effectively crossing the

blood‐brain barrier in the intracranial xenograft model of central

nervous system lymphoma.

Degradation of Ikaros/Aiolos by CC‐99282 in T cells correlated

with increased secretion of IL‐2, a hallmark of immune activation.

CC‐99282 was able to reverse T‐cell exhaustion and induce secretion

of the effector cytokines/chemokines GM‐CSF, IFNγ, and TNFα, at

concentrations (0.1–100 nM) that induced strong antitumor effects

in vitro.

Conclusions: CC‐99282 is a novel CELMoD that, compared with LEN

and other immunomodulatory agents, shows enhanced anti-

proliferative, apoptotic, and immune‐stimulatory activity in a range of

DLBCL models, including those with acquired chemoresistance.

These data support the clinical investigation of CC‐99282 in patients

with R/R NHL.

FIGURE:

ANTITUMOR ACTIVITY OF CC‐99282 IN A WSU‐DLCL2

DLBCL XENOGRAFT MODEL. FEMALE SCID MICE, INOCULATED

WITH 10 � 10

WSU‐DLCL2 TUMORC CELLS INTO THE FLANK,

WHERE RANDOMIZED INTO TREATMENT GROUPS (N = 9/GROUP)

AT TREATMENT INITIATION. TEST ARTICLE TREATMENT STARTED

ON D18 WHEN TUMORS WHERE APPROXIMATELY 350 MM

. THE

5D ON/2D OFF REPRESENTS QD DOSING FOR 5 CONSECUTIVE

DAYS FOLLOWED BY 2 DAYS OFF. THE CHOP SINGLE‐CYCLE

SCHEDULE ENTAILED CYCLOPHOSPHAMIDE (40 MG/KG),

DOXORUBICIN (3.3 M/KG), ADMINISTERED PO ON D 1‐5 BEGIN-

NING ON D1 OF TREATMENT. RESULTS ARE PRESENTED AS MEAN

VALUES WITH ERROR BARS REPESENTS TUMOR FREE. CHOP,

CYCLOPHOSPHAMIDE DOXORUBICIN, VINBLASTINE, AND

PREDNISONE; D,DAY; DLBCL, DIFFUSE LARGE B‐CELL LYM-

PHOMA; IV, INTRAVENOUSLY; PO, ORALLY; QD, DAILY; SEM,

STANDARD ERROR OF THE MEAN

The research was funded by: Bristol Myers Squibb

Keywords: Molecular Targeted Therapies

Conﬂicts of interests pertinent to the abstract

A. Lopez‐Girona

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

L. Groocock

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

Z. Mo

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

R. K. Narla

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

P. Janardhanan

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

S. Wood

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

D. Mendy

Employment or leadership position: Bristol Myers Squibb

L. Barnes

Employment or leadership position: Bristol Myers Squibb

S. Peng

Employment or leadership position: Bristol Myers Squibb

D. Jankeel

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

C. Fontanillo

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

S. Carrancio

Employment or leadership position: Bristol Myers Squibb

Stock ownership: Bristol Myers Squibb

J. Hansen

Employment or leadership position: Bristol Myers Squibb

233 | CFT7455: A NOVEL, IKZF1/3 DEGRADER THAT

DEMONSTRATES POTENT TUMOR REGRESSION IN A SPECTRUM

OF NHL XENOGRAFT MODELS

S. Perino

, B. Class

, C. Henderson

, M. Isasa

, R. J. Kirby

, R. V.

Agafonov

, P. Chaturvedi

, S. J. Eron

, A. Good

, A. A. Hart

, J. A.

316

SUPPLEMENT ABSTRACTS

Henderson

, B. T. Kreger

, M. Mahler

, R. M. Pollock

, A. S. Crystal

C. G. Nasveschuk

, S. L. Fisher

, D. A. Proia

C4 Therapeutics, Discovery, Watertown, Massachusetts, USA

Introduction: Ikaros family zinc ﬁnger protein 1 and 3 (IKZF1/3) are

essential transcription factors (TF) for differentiation of B and T

lymphocytes. IMiDs (e.g. pomalidomide (pom)) degrade IKZF1/3 via

interaction with the cereblon (CRBN) E3 ligase and have shown

promise in NHL. Preclinical data suggest improvements in IKZF1/3

degraders may lead to enhanced efﬁcacy. CFT7455 is a novel IKZF1/

3 degrader optimized for high afﬁnity CRBN binding and IKZF1/3

degradation, resulting in downregulation of the interferon regulatory

factor 4 (IRF4), a critical regulator in non‐Hodgkin's lymphoma

(NHL), including diffuse large B‐cell lymphoma (DLBCL), mantle cell

lymphoma (MCL) and peripheral T‐cell lymphoma (PT).

Methods: Protein expression in cell lines and tumor xenografts were

quantiﬁed by immunoassays or targeted mass spectrometry. Binding

afﬁnity was determined by ﬂuorescence polarization or cellular

NanoBRET assays. Cell viability were monitored by CellTiter‐Glo.

Tumor xenograft studies were conducted by implanting human NHL

lines into immunocompromised mouse strains.

Results: CFT7455's potency as a CRBN binder is evident from cellular

CRBN competition studies (IC50 = 0.4 nM). In the ALK+ anaplastic

large cell lymphoma (ALCL) line KiJK, CFT7455 treatment led to >80%

degradation of IKZF1, which was blocked by proteasome or NEDD8

inhibition, demonstrating on mechanism activity. CFT7455 demon-

strated potent antiproliferative activity across a panel of NHL cell lines.

In KiJK xenografts, pom treatment was ineffective at a clinically

relevant dose (3000 µg/kg/day). CFT7455 treatment (100 µg/kg/day,

PO) resulted in durable tumor regression associated with deep IKZF3

degradation and IRF4 downregulation (7% and 25% remaining,

respectively). CFT7455 showed dose dependent efﬁcacy in the ALK‐

ALCL xenograft model, DL40, from 3‐100 µg/kg with regressions at

doses ≥10 µg/kg. Global proteomic studies on DL40 xenografts

treated with CFT7455 (100 µg/kg, 4 hours) showed only IKZF1/3

were signiﬁcantly degraded.

MCL is characterized by elevated cyclin D1, subsequent release

of E2F1 and pathway activation. In the REC1 MCL xenograft model,

doses of CFT7455 ≥10 µg/kg promoted tumor regression. Pharma-

codynamic studies showed that CFT7455 (30 µg/kg) promoted

degradation of IKZF3 and downregulation of cyclin D1 and E2F1.

In a pom insensitive DLBCL model (TMD8), administration of

CFT7455 (100 µg/kg) led to tumor regression. Together these results

show that the optimized CRBN binding and catalytic activity of

CFT7455 results in rapid, deep and sustained degradation of IKZF1/3

and translates to tumor regressions in NHL models.

Conclusions: CFT7455 is a potent, selective catalytic degrader of

IKZF1/3, with single agent antitumor activity in DLBCL, ALCL, and

MCL models including those insensitive to pom. These results sup-

port clinical investigation of CFT7455 for NHL.

Keywords: Molecular Targeted Therapies, Aggressive B‐cell non‐

Hodgkin lymphoma, Aggressive T‐cell non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

S. Perino

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

B. Class

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

C. Henderson

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

M. Isasa

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

R. J. Kirby

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

R. V. Agafonov

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

P. Chaturvedi

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

S. J. Eron

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

A. Good

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

A. A. Hart

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

J. A. Henderson

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

B. T. Kreger

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

M. Mahler

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

R. M. Pollock

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

SUPPLEMENT ABSTRACTS

317

A. S. Crystal

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

C. G. Nasveschuk

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

S. L. Fisher

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

D. A. Proia

Employment or leadership position: C4 Therapeutics

Stock ownership: C4 Therapeutics

234 | GLYCOPROTEIN PTGDS ACTS AS A POTENTIAL TARGET

IN DIFFUSE LARGE B‐CELL LYMPHOMA BY REGULATING MYH9‐

WNT‐β‐CATENIN/STAT3 AXIS

S. Hu

, X. Zhou

, S. Ren

, Y. Cai

, J. Liu

, Y. Han

, Y. Zhao

, J. Yang

X. Wang

Shandong Provincial Hospital Afﬁliated to Shandong University,

Department of Hematology, Jinan, China

Introduction: Glycoprotein prostaglandin D2 Synthase (PTGDS) is a

member of lipocalin superfamily and AT56 is its selective inhibitor.

PTGDS has been involved in several cellular processes, yet its func-

tion and mechanism in carcinogenesis remains ill deﬁned. Herein, we

aimed to investigate the functional signiﬁcance of PTGDS and pro-

posed a novel therapeutic strategy in diffuse large B‐cell lymphoma

(DLBCL).

Methods: Lymph node biopsies from 53 DLBCL patients and 28

reactive hyperplasia cases were obtained with informed consents.

CD19

magnetic microbeads were used to purify CD19

B cells.

Lentivirus tranfection was performed to stably knockdown or over-

express PTGDS. CoIP and mass spectrometry were used to investi-

gate molecular mechanism. Glycosylation sites were veriﬁed by point

mutations. Xenograft model was established and BALB/c nude mice

were imaged using In‐Vivo small animal imaging system.

Results: Bioinformatics analysis showed that PTGDS was upregu-

lated in DLBCL based on Oncomine database. High expression of

PTGDS protein was found in DLBCL tissues and serum, which was

correlated with poor prognosis.

PTGDS overexpression and rhPTGDS caused increased cell

proliferation. PTGDS knockdown and AT56 signiﬁcantly inhibited cell

proliferation and invasion, promoted cell cycle arrest and cell

apoptosis. PTGDS inhibition also enhanced sensitivity to Bend-

amustine and Adriamycin. Besides, in vivo studies showed PTGDS

knockdown and AT56 exerted anti‐tumor effect in DLBCL.

PTGDS was found to interact with oncogenic factor, MYH9

through CoIP and mass spectrometry. The expression of MYH9 was

decreased by PTGDS inhibition, which also inhibited activation of

Wnt‐β‐catenin/STAT3 pathway. Besides, Wnt3a could rescue the

inhibitory role of AT56 on malignant behaviors, including cell pro-

liferation, cell cycle arrest and cell apoptosis. Moreover, the effect of

AT56 on Wnt pathway could also be reversed by Wnt3a. WP1066

could reverse enhanced proliferation caused by PTGDS over-

expression, and the inhibited proliferation and increased apoptosis

caused by AT56 were enhanced by WP1066. Both the proliferation

promotion and the activation of Wnt‐β‐catenin/STAT3 pathway by

PTGDS overexpression was restored by Blebbistatin.

The N‐glycosylation of PTGDS protein in Asn 51 and Asn78 was

veriﬁed and abnormal glycosylation resulted in nuclear translocation,

prolonged half time and enhanced oncogenic role.

Conclusions: Our data ﬁrstly identiﬁed the oncogenic role of

PTGDS in DLBCL. High PTGDS expression was associated with

prognosis of DLBCL patients. Moreover, in vitro and in vivo studies

indicated that PTGDS inhibition exerted anti‐tumor effect by

regulating MYH9‐Wnt‐β‐catenin/STAT3 axis. This study indicates

that PTGDS acts as a potential molecular target for DLBCL

treatment and highlights the potential role of AT56 as a novel

therapeutic strategy for DLBCL.

The research was funded by: National Natural Science Foundation

(No.82070203, No.81770210, No.81473486 and No.81270598); Key

Research and Development Program of Shandong Province

(No.2018CXGC1213); Technology Development Projects of

FIGURE 1

318

SUPPLEMENT ABSTRACTS

Shandong Province (No.2017GSF18189); Translational Research

Grant of NCRCH (No.2021WWB02, No.2020ZKMB01); Taishan

Scholars Program of Shandong Province; Shandong Provincial Engi-

neering Research Center of Lymphoma; Academic Promotion Pro-

gramme of Shandong First Medical University (No. 2019QL018).

Keywords: Genomics, Epigenomics, and Other ‐Omics,

Molecular Targeted Therapies, Aggressive B‐cell non‐Hodgkin

lymphoma

No conﬂicts of interest pertinent to the abstract.

FIGURE 3

FIGURE 2

FIGURE 4

SUPPLEMENT ABSTRACTS

319

235 | CLINICAL APPLICATION OF AN EX‐VIVO PLATFORM TO

GUIDE THE CHOICE OF DRUG COMBINATIONS IN RELAPSED/

REFRACTORY LYMPHOMA; A PROSPECTIVE STUDY

S. De Mel

, J. Goh

, M. B. M. A. Rashid

, X. Y. Zhang

, P. Jaynes

, X. Liu

L. Poon

, E. Chan

, J. Lee

, Y. L. Chee

, L. P. Koh

, L. K. Tan

, T. G. Soh

, Y.

C. Yuen

, Hoi‐Y. Loi

, Siok‐B. Ng

, X. Goh

, D. Tan

, D. M. Z. Cheah

, W.

L. Pang

, D. Huang

, J. Y. Chan

, N. Somasundaram

, T. Tang

, S. T.

Lim

, C. K. Ong

, W.‐J. Chng

, E. K. Chow

, A. D. Jeyasekharan

National University Health System, Department of Haematology‐

Oncology, National University Cancer Institute, Singapore, Singapore,

Singapore,

National University of Singapore, Cancer Science Institute of

Singapore, Singapore, Singapore,

KYAN Therapeutics, Singapore,

Singapore,

National University Hospital, Department of Laboratory

Medicine, Singapore, Singapore,

National University Health System,

Department of Pharmacy, Singapore, Singapore,

National University

Hospital Singapore, Department of Diagnostic Imaging, Singapore,

Singapore,

National University of Singapore, Department of Pathology,

Yong Loo Lin School of Medicine, Singapore, Singapore,

National Uni-

versity Hospital, Department of Otorhinolaryngology, Singapore,

Singapore,

Mt Elizabeth Hospital, Dr Daryl Tan Clinic for Lymphoma,

Myeloma and Blood Disorders, Singapore, Singapore,

National Cancer

Centre Singapore, Lymphoma Genomic Translational Research Labora-

tory, Division of Cellular and Molecular Research, Singapore, Singapore,

National Cancer Centre Singapore, Division of Medical Oncology,

Singapore, Singapore,

National Cancer Centre Singapore, Division of

Cellular and Molecular Research, Singapore, Singapore

Introduction: While combination therapy is the standard of care for

relapsed/ refractory non‐Hodgkin lymphoma (RR‐NHL), the choice of

combinations for an individual patient is empirical, and response rates

remain poor. Here we explore the use of a hybrid experimental/ana-

lytic method termed Quadratic Phenotypic Optimization Platform

(QPOP), for prediction of optimal drug combinations from limited

clinical material. This high‐throughput platform identiﬁes optimal

drug‐combinations on ex‐vivo biopsies using an orthogonal array

composite design to maximise search space. These features are

potentially useful to assess personalized efﬁcacious combinations

among a set of drugs with single agent pre‐clinical or clinical activity in

lymphoma.

Methods: We performed a prospective cohort study of QPOP analysis

in RR‐NHL. Participants included RR‐NHL patients across two tertiary

oncology centres in Singapore, with disease amenable to biopsy or

blood/ marrow aspiration, recruited between 1

November 2017 and

August 2020‐ with a median follow up of 20 months. QPOP drug

combination scores were derived from lymphoma samples (approxi-

mately 1,000,000 cells/ patient) using a matrix of drugs with known

pre‐clinical or clinical efﬁcacy against NHL. Results were shared with

the treating physician, and off‐label QPOP‐guided therapy was offered

in the absence of standard options. The primary outcomes were

feasibility and turnaround time of QPOP analysis. The secondary

outcomes were identiﬁcation of recurrent 2 and 3 drug‐combinations,

and concordance of QPOP results with clinical responses.

Results: In this interim analysis period, we recruited 36 patients

comprising 19 B‐NHL, 15 T/NK‐NHL and 2 composite lymphomas

(CL), with a median age of 57.5 years and median 2 prior lines of

FIGURE 6

FIGURE 5

320

SUPPLEMENT ABSTRACTS

treatment. Successful QPOP analysis (Z’ score >0.5) was feasible in

31/36 cases with an average turn‐around time of 5.7 (±2.1) days.

QPOP predicted frequent sensitivities to Copanlisib‐based combina-

tions in B‐NHL (n = 7/12), and Romidepsin‐based combinations in T/

NK‐NHL (4/11). Importantly, efﬁcacy of speciﬁc combinations was not

entirely dependent on single agent dose responses. Clinical responses

after standard‐of‐care (n = 15) or QPOP‐derived regimens (n = 5) was

evaluable for 20 independent treatments in 17/31 patients. QPOP

had a positive predictive value of 100% and a negative predictive

value of 80% for response (n = 20, p = 0.008), and an AUC of 0.838

(95%CI 0.626‐1.051; p = 0.011). Complete responses were achieved

with novel drug combinations, including Palbociclib‐Everolimus for B‐

NHL and Romidepsin‐Bortezomib for T/NK‐NHL.

Conclusions: Prediction of sensitivity to drug‐combinations in a clini-

cally applicable time‐frame is feasible for RR‐NHL cases

through QPOP analysis. QPOP was also able to identify novel clinically

effective combinations in patients refractory to standard therapy.

The research was funded by: Funding for all aspects of the project

was provided by the Singapore Ministry of Health's National Medical

Research Council 'Singapore lYMPHoma translatiONal studY (SYM-

PHONY)' Open Fund Large Collaborative Grant (MOH‐000205‐03).

Keywords: Combination Therapies, Aggressive B‐cell non‐Hodgkin

lymphoma, Aggressive T‐cell non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

S. De Mel

Other remuneration: SDM is an inventor on a patent for QPOP titled

‘Method For Predicting A Suitable Therapy’ (Patent Cooperation

Treaty (PCT) Application No.: PCT/SG2020/050595).

M. B. M. A. Rashid

Other remuneration: MBMAR is an inventor on a patent for QPOP

titled ‘Method For Predicting A Suitable Therapy’ (Patent Coopera-

tion Treaty (PCT) Application No.: PCT/SG2020/050595).

W.‐J. Chng

Honoraria: Amgen, J&J, Celgene, BMS, Abbvie, Novartis, Takeda

Research funding: J&J, Celgene, Hummingbird

Other remuneration: WJC is an inventor on a patent for QPOP titled

‘Method For Predicting A Suitable Therapy’ (Patent Cooperation

Treaty (PCT) Application No.: PCT/SG2020/050595)

E. K. Chow

Employment or leadership position: KYAN Therapeutics

Stock ownership: KYAN Therapeutics

Other remuneration: EKC is an inventor on a patent for QPOP titled

‘Method For Predicting A Suitable Therapy’ (Patent Cooperation

Treaty (PCT) Application No.: PCT/SG2020/050595).

A. D. Jeyasekharan

Consultant or advisory role: Turbine Ltd, AstraZeneca, Janssen and

MSD

Research funding: Janssen and AstraZeneca.

Educational grants: Perkin Elmer

Other remuneration: ADJ is an inventor on a patent for QPOP titled

‘Method For Predicting A Suitable Therapy’ (Patent Cooperation

Treaty (PCT) Application No.: PCT/SG2020/050595).

236 | TG‐1701, A SELECTIVE BRUTON TYROSINE KINASE (BTK)

INHIBITOR, AS MONOTHERAPY AND IN COMBINATION WITH

UBLITUXIMAB AND UMBRALISIB (U2) IN PATIENTS WITH B‐CELL

MALIGNANCIES

C. Y. Cheah

, W. Jurczak

, M. Lasica

, N. Wickham

, T. Wróbel

, J.

Walewski

, C. K. Yannakou

, S. Cheung

, K. L. Lewis

, M. Długosz‐

Danecka

, K. Giannopoulos

, H. P. Miskin

, J.‐P. Tang

, E. Normant

O. A. O'Connor

, A. D. Ricart

, C. S. Tam

Sir Charles Gairdner Hospital, Department of Haematology, Perth,

Australia,

Maria Sklodowska‐Curie National Research Institute of

Oncology, Oncology Center, Krakow, Poland,

St. Vincent Hospital and

University of Melbourne, Haematology, Melbourne, Australia,

Ashford

Cancer Centre Research, Hematology, Adelaide, Australia,

Wroclaw

Medical University, Department of Haematology, Blood Neoplasms and

Bone Marrow Transplantation, Wroclaw, Poland,

Maria Sklodowska‐

Curie National Research Institute of Oncology, Department of Lymphoid

Malignancy, Warsaw, Poland,

Epworth HealthCare, Department of Mo-

lecular Oncology and Cancer Immunology, East Melbourne, Australia,

John's Cancer Centre, Hematology Department, Lublin, Poland,

Therapeutics, Oncology, New York, USA

Introduction: TG‐1701 is a selective, covalent BTK inhibitor

administered once daily (QD). Both the “U2” combination (anti‐CD20

mAb ublituximab + the PI3Kδ‐CK1ε inhibitor umbralisib) and BTK

inhibition are highly active in treatment‐naïve (TN) and relapsed/

refractory (R/R) CLL, each having previously demonstrated

superiority over standard chemoimmunotherapy. Herein we report

the results of the dose escalation of TG‐1701 monotherapy and TG‐

1701+U2.

Methods: Patients (pts) with R/R CLL, MCL and Waldenström's (WM)

were enrolled in an ongoing Ph 1 study initially evaluating dose

escalation (DE) of oral TG‐1701 QD continuously administered in 28‐

day cycles (100, 200, 300, and 400 mg). After characterizing the

safety proﬁle of TG‐1701 monotherapy, we implemented a parallel

DE arm of TG‐1701+U2. Select dose levels of TG‐1701 monotherapy

were expanded. All pts were treated until disease progression, un-

acceptable toxicity, or investigator/patient decision to withdraw.

Results: As of 03 February 2021, 123 pts were treated with TG‐

1701 as follows: 25 in the monotherapy DE arm, 61 in the 200

mg disease‐speciﬁc cohorts (20 CLL [5 TN], 21 MCL [4 TN], 20

WM [8 TN]), 20 in the 300 mg CLL cohort (4 TN), and 17 in the

1701+U2 DE arm. The median # of prior therapies was 1 (range, 1

‐ 10). All pts were BTKi‐naïve. All 123 pts were evaluable for

safety. TG‐1701 was well tolerated and the maximum tolerated

dose (MTD) for monotherapy was not reached at 400 mg

(demonstrating near 100% saturation of the BTK at all dose levels

studied). Treatment emergent adverse events (TEAE) of clinical

SUPPLEMENT ABSTRACTS

321

interest included atrial ﬁbrillation (AF 4.0% of pts, G ≥3 in 1 case),

G ≥3 hypertension (2.4%), and bleeding events (18.7%, all G1‐2).

No cases of ventricular tachyarrhythmia were reported. TEAEs

leading to TG‐1701 dose reduction occurred in 6.5% of pts. TEAEs

leading to treatment discontinuation occurred in 1.6% of pts (AF,

COVID‐19). At the data cut‐off, 119 pts were evaluable for

response, including 40 in DE (Table). The median duration of

response has not been reached among responders overall. The

median follow‐up (mFU range) was 15.9 mos (1.3 ‐ 28.6+) in DE

and 8.5 mos (1.4 ‐15.6+) in disease‐speciﬁc cohorts. Best change

from baseline in tumor burden in pts in the 1701+U2 combination

arm is presented in the ﬁgure below.

Conclusions: TG‐1701 exhibits an encouraging safety and efﬁcacy

proﬁle. The combination of 1701+U2 has been well tolerated and

dose escalation continues. The combination shows enhanced depth of

response over TG‐1701 monotherapy. Recruitment to this study

(NCT03671590) continues.

EA – previously submitted to EHA 2021.

The research was funded by: TG Therapeutics Inc.

Keywords: Chronic Lymphocytic Leukemia (CLL), Molecular Targeted

Therapies, Combination Therapies

Conﬂicts of interests pertinent to the abstract

C. Y. Cheah

Employment or leadership position: None

Consultant or advisory role: Janssen‐Cilag, Roche/Genentech, TG

Therapeutics, Loxo/Lilly, Gilead Sciences, AstraZeneca, Bristol‐Myers

Squibb, Ascentage Pharma, MDS

Stock ownership: None

Honoraria: Roche/Genentech, Janssen‐Cilag, TG Therapeutics, Loxo/

Lilly, AstraZeneca, Bristol‐Myers Squibb, Gilead Sciences, Ascentage

Pharma, MDS

Research funding: Roche, Celgene, AbbVie

Other remuneration: Travel, Accommodations, Expenses: Roche

W. Jurczak

Employment or leadership position: None

Consultant or advisory role: MEI Pharma, Debiopharm, Loxo, Takeda,

AstraZeneca, BeiGene

Stock ownership: None

Honoraria: None

Research funding: GlaxoSmithKline You Acerta Pharma You Astra-

Zeneca You Nordic Nanovector You Incyte You DebiopGenentech,

Janssen, Loxo, MEI Pharma, MorphoSys, Takeda, TG Therapeutics,

BeiGene

Educational grants: None

Other remuneration: None

T. Wróbel

Employment or leadership position: None

Consultant or advisory role: Roche/Genentech, Abbvie, Takeda,

Novartis, Janssen‐Cilag, Amgen

Stock ownership: None

Honoraria: Celgene, Roche, Gilead Sciences, Amgen, Janssen‐Cilag

Research funding: Roche

Educational grants: None

Other remuneration: None

J. Walewski

Employment or leadership position: None

Consultant or advisory role: Roche, Abbvie, Takeda/Millennium,

Gilead Sciences, Novartis

Stock ownership: None

Honoraria: Roche, Abbvie, Servier, Amgen, Takeda/Millennium,

Gilead Sciences, Novartis

Research funding: None

Educational grants: Roche

Other remuneration: None

S. Cheung

Employment or leadership position: None

Consultant or advisory role: Novartis

Stock ownership: None

Honoraria: None

Research funding: None

Educational grants: None

Other remuneration: None

K. L. Lewis

Employment or leadership position: None

Consultant or advisory role: Roche

Stock ownership: None

TABLE Response per investigator review by treatment group

DE arm

(N = 23)

200 mg CLL

(N = 20)

200 mg MCL

(N = 20)

200 mg WM

(N = 20)

300 mg CLL

(N = 19)

1701+U2 DE arm

(N = 17)

ORR, % 56.5 95.0 60.0 95.0 100 82.3

CR, % 0 0 0 0 0 23.5

Very good PR, % 4.3 0 5.9

PR, % 47.8 95.0 60.0 70.0 100 52.9

Minor response, % 4.3 25.0 0

mFU mos 17.5 11.6 8.2 9.7 5.8 14.3

322

SUPPLEMENT ABSTRACTS

Honoraria: Janssen, Novartis

Research funding: None

Educational grants: Janssen, Novartis

Other remuneration: None

M. Długosz‐Danecka

Employment or leadership position: None

Consultant or advisory role: Servier, Abbvie

Stock ownership: None

Honoraria: None

Research funding: None

Educational grants: None

Other remuneration: Speakers' Bureau: Janssen, Servier, Roche,

Takeda.

K. Giannopoulos

Employment or leadership position: None

Consultant or advisory role: Abbvie, Bristol‐Myers Squibb/Celgene,

Sanoﬁ, Takeda, Amgen

Stock ownership: None

Honoraria: Janssen, Bristol‐Myers Squibb/Celgene, Sanoﬁ, Takeda,

Amgen.

Research funding: TG Therapeutics, Abbvie, Bristol‐Myers Squibb/

Celgene, Sanoﬁ, Takeda, Amgen.

Educational grants: None

Other remuneration: None

H. P. Miskin

Employment or leadership position: TG Therapeutics

Consultant or advisory role: None

Stock ownership: TG Therapeutics

Honoraria: None

Research funding: None

Educational grants: TG Therapeutics

Other remuneration: None

J.‐P. Tang

Employment or leadership position: TG Therapeutics

Consultant or advisory role: None

Stock ownership: TG Therapeutics, Roche, Alexion Pharmaceuticals

Honoraria: None

Research funding: None

Educational grants: None

Other remuneration: None

E. Normant

Employment or leadership position: TG Therapeutics

Consultant or advisory role: None

Stock ownership: TG Therapeutics, Surface Oncology

Honoraria: None

Research funding: None

Educational grants: None

Other remuneration: None

O. A. O'Connor

Employment or leadership position: TG TherapeuticsTG, Kymera,

NomoCan

Consultant or advisory role: Kymera, Celgene, Mundipharma,

SERVIER

Stock ownership: TG Therapeutics, Kymera.

Honoraria: Kymera, Celgene, Astex Pharmaceuticals

Research funding: Celgene, Astex Pharmaceuticals, Merck

Educational grants: None

Other remuneration: None

A. D. Ricart

Employment or leadership position: TG Therapeutics

Consultant or advisory role: None

Stock ownership: Pﬁzer, Merck, TG Therapeutics, Seattle Genetics,

Collegium, Immunomedics, Stemline Therapeutics

Honoraria: None

Research funding: None

Educational grants: None

Other remuneration: None

C. S. Tam

Employment or leadership position: None

Consultant or advisory role: Janssen, Loxo, Roche, BeiGene, Abbvie

Stock ownership: None

Honoraria: Janssen‐Cilag, Abbvie, Novartis, Beigene, Pharmacyclics

Research funding: Janssen‐Cilag, Abbvie

Educational grants: None

Other remuneration: None

237 | FIRST‐MIND: A PHASE IB, OPEN‐LABEL, RANDOMIZED

STUDY TO ASSESS SAFETY OF TAFASITAMAB OR TAFASITAMAB

+ LENALIDOMIDE IN ADDITION TO R‐CHOP IN PATIENTS WITH

NEWLY DIAGNOSED DLBCL

D. Belada

, K. Kopeckova

, J. M. Bergua Burgues

, M. André

, E.

Pérez Persona

, P. Pichler

, P. Klöpfer

, B. Brackertz

, E. Lohrmann

A. Lahiry

, N. Shah

, W. Brugger

, J. M. Burke

, G. S. Nowakowski

University Hospital and Faculty of Medicine, 4th Department of Internal

Medicine – Hematology, Hradec Králové, Czech Republic,

2nd Faculty of

Medicine, Charles University and Motol University Hospital, Department

of Oncology, Prague, Czech Republic,

Hospital San Pedro de Alcantara,

Hematology, Cáceres, Spain,

Université Catholique de Louvain,

Department of Haematology, CHU UCL Namur, Yvoir, Belgium,

Osakidetza Basque Health Service, Araba University Hospital,

Hematology, Vitoria‐ Gasteiz, Spain,

University Hospital of St.

Pölten, Department of Internal Medicine, St. Pölten, Austria,

MorphoSys

AG, Clinical Development, Planegg, Germany,

MorphoSys AG, Global

Patient Safety, Planegg, Germany,

MorphoSys AG, Biostatistics and Data

Management, Planegg, Germany,

US Oncology Research and Rocky

Mountain Cancer Centers, Hematology, Aurora, Colorado, USA,

Mayo

Clinic, Division of Hematology, Rochester, MN, USA

SUPPLEMENT ABSTRACTS

323

Introduction: Tafasitamab is a humanized, Fc‐modiﬁed, anti‐CD19

monoclonal antibody that enhances antibody‐dependent cellular

cytotoxicity and phagocytosis. It is FDA‐approved in combination

with lenalidomide (LEN) for adult patients (pts) with relapsed/re-

fractory diffuse large B‐cell lymphoma (R/R DLBCL) ineligible for

autologous stem cell transplant. First‐MIND (NCT04134936) is a

Phase Ib, open‐label, randomized study to assess the safety and

preliminary efﬁcacy of tafasitamab + R‐CHOP or tafasitamab + LEN

+ R‐CHOP in pts with newly diagnosed DLBCL.

Methods: Eligible pts were ≥18 years old, treatment (Tx)‐naïve,

with DLBCL, international prognostic index (IPI) 2–5 and ECOG

performance status (PS) 0–2. Pts with known double‐ or triple‐hit

and transformed lymphoma were excluded. Tx included six 21‐day

[D] cycles of R‐CHOP + tafasitamab (12 mg/kg IV, D1, 8, 15) (arm

A) or R‐CHOP + tafasitamab (12 mg/kg IV, D1, 8, 15) + LEN (25

mg orally, D1–10) (arm B). G‐CSF and VTE prophylaxis was

mandatory. The primary objective was safety; secondary objectives

included overall response rate (ORR) and PET‐CR rate at end of

Tx, progression‐free survival, long‐term safety, pharmacokinetics

and immunogenicity.

Results: From Dec 2019 to Aug 2020, 83 pts were screened in nine

countries across Europe and the US; 66 were randomized (arm A,

n = 33; arm B, n = 33). Data cut‐off: Dec 9, 2020 (study ongoing).

Median age was 64.5 years (range 20–86). Overall, 30% of pts (20/66)

were ≥70 years old and many had high‐risk disease: IPI 2: 28.8%, IPI 3:

45.5%, IPI 4: 25.8%; ECOG PS 0: 47.0%, PS 1: 43.9%, PS 2: 9.1%. Most

pts had stage III/IV disease (92%); 45.5% had bulky disease.

All pts experienced a treatment‐emergent adverse event (TEAE).

Grade ≥3 neutropenia and thrombocytopenia occurred in 54.5% and

12.1% (arm A), and 66.7% and 30.3% (arm B) of pts, respectively. Six pts

in each arm experienced febrile neutropenia. Grade ≥3 nervous system

disorders occurred in 6.1% of pts in arm A and 12.1% in arm B (most

events were polyneuropathies related to vincristine). Infusion‐related

reactions to both rituximab and tafasitamab occurred in 12.1% (arm A)

and 18.2% (arm B) of pts, and 21.2% (arm A) and 27.3% (arm B) had a

Grade ≥3 infection and/or infestation (TEAEs by system organ class

FIGURE 1 TEAEs by system organ class and toxicity grade

324

SUPPLEMENT ABSTRACTS

shown in Figure 1). Serious TEAEs occurred in 42.4% (arm A) and 51.5%

(arm B) of pts. There were three deaths unrelated to tafasitamab and/

or LEN (sepsis, urosepsis, and COVID‐19 pneumonia). Dose intensity of

R‐CHOP was maintained in both arms.

Among 60 pts who completed tumor assessments after cycle 3,

ORR was 89.7% (arm A) and 93.5% (arm B).

Conclusion: These data suggest that R‐CHOP + tafasitamab or

tafasitamab + LEN is tolerable in pts with Tx‐naïve DLBCL. Dosing of

R‐CHOP is unaffected by the addition of tafasitamab. Toxicities were

similar to those expected with R‐CHOP alone or with LEN. Updated

safety and early efﬁcacy data will be presented at the conference.

EA – previously submitted to ASCO and EHA 2021.

The research was funded by: MorphoSys AG, Planegg, Germany

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma

Conﬂicts of interests pertinent to the abstract

D. Belada

Consultant or advisory role: Roche, Gilead Sciences, Janssen‐Cilag,

Takeda, MorphoSys AG, Debiopharm Group

Research funding: Roche, Gilead Sciences, Janssen‐Cilag, Takeda,

MorphoSys AG, Pharmacyclics, Archigen Biotech, Dr Reddy's

Laboratories

Educational grants: Gilead Sciences, Takeda, Roche

E. Pérez Persona

Consultant or advisory role: Celgene/BMS, Amgen, Janssen, GSK

Educational grants: Roche, Celgene/BMS, Amgen, Janssen, Abbvie,

Jazz Pharmaceutical

Other remuneration: Roche, Celgene/BMS, Amgen, Janssen, Abbvie.

Takeda, Sanoﬁ

P. Klöpfer

Employment or leadership position: MorphoSys AG

B. Brackertz

Employment or leadership position: MorphoSys AG

E. Lohrmann

Employment or leadership position: MorphoSys AG

A. Lahiry

Employment or leadership position: MorphoSys AG

N. Shah

Employment or leadership position: MorphoSys AG

W. Brugger

Employment or leadership position: MorphoSys AG

J. M. Burke

Consultant or advisory role: Genentech/Roche, AbbVie, Seattle Ge-

netics, Bayer, AstraZeneca, Adaptive Biotechnologies, Verastem,

MorphoSys AG, Kura, Epizyme, BeiGene, Kymera

Other remuneration: Seattle Genetics, Beigene

G. S. Nowakowski

Consultant or advisory role: Celgene, MorphoSys AG, Genentech,

Selvita, Debiopharm Group, Kite/Gilead Sciences

Research funding: Celgene, NanoString Technologies, MorphoSys AG

238 | CLINICAL ACTIVITY OF LONCASTUXIMAB TESIRINE

PLUS IBRUTINIB IN NON‐HODGKIN LYMPHOMA: UPDATED

LOTIS 3 PHASE 1 RESULTS

J. Depaus

, N. Wagner‐Johnston

, P. L. Zinzani

, T. J. Phillips

, J.

Maly

, S. Ferrari

, E. Bachy

, L. J. Bryan

, V. Delwail

, M. Janakiram

S. de Guibert

, M. Tani

, V. Dai

, K. Havenith

, J. Boni

, X. He

A. Ervin‐Haynes

, C. Carlo‐Stella

CHU UCL Namur site Godinne, Department of Hematology, Yvoir, Belgium,

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins

University School of Medicine, Division of Oncology, Baltimore, Maryland,

USA,

Università di Bologna, IRCCS Azienda Ospedaliero‐Universitaria di

Bologna Istituto di Ematologia "Seràgnoli", and Dipartimento di Medicina

Specialistica, Diagnostica e Sperimentale, Bologna, Italy,

University of

Michigan, Comprehensive Cancer Center, Ann Arbor, USA,

Norton Cancer

Institute, Medical Oncology, Louisville, Kentucky, USA,

Azienda Ospeda-

liera Papa Giovanni XXIII, Hematology and Bone Marrow Transplant Unit,

Bergamo, Italy,

Hôpital Lyon Sud, Department of Hematology, Pierre‐

Bénite, France,

Georgia Cancer Center at Augusta University, Department

of Medicine, Division of Hematology/Oncology, Augusta, Georgia, USA,

Centre Hospitalier Universitaire de Poitiers, Department of Hematology

and Cell Therapy, Poitiers, France,

University of Minnesota, Division of

Hematology, Oncology and Transplantation, Minneapolis, Minnesota, USA,

Centre Hospitalier Universitaire de Rennes Hôpital Pontchaillou,

Department of Clinical Hematology, Rennes, France,

Santa Maria delle

Crioci Hospital, Unit of Hematology, Ravenna, Italy,

ADC Therapeutics

America, Inc, Clinical Development, Murray Hill, New Jersey, USA,

ADC

Therapeutics (UK) Ltd, Research and Development, London, UK,

Humanitas Clinical and Research Center – IRCCS, and Humanitas Uni-

versity, Department of Oncology and Hematology, Rozzano, Milan, Italy

Introduction: The treatment of relapsed/refractory (R/R) diffuse

large B‐cell lymphoma (DLBCL) and mantle cell lymphoma (MCL)

remains an area of unmet need. Combination therapy using agents

with different mechanisms of action may improve upon therapeutic

outcomes. We investigated the combination of loncastuximab tesir-

ine (Lonca; an antibody‐drug conjugate composed of a humanized

anti‐CD19 monoclonal antibody conjugated to a pyrrolobenzodiaze-

pine dimer toxin) with ibrutinib (a small‐molecule inhibitor of Bru-

ton's tyrosine kinase). Here we present updated safety and efﬁcacy

data from the Phase 1 portion of a Phase 1/2 study (NCT03684694).

Methods: The protocol is a dose escalation and dose expansion, open

label, single‐arm, combination study in patients (≥18 years) with R/R

DLBCL or R/R MCL. The primary objectives of Phase 1 are to char-

acterize the safety and tolerability of Lonca plus ibrutinib, and identify

the recommended Phase 2 dose and schedule. Secondary objectives

include evaluation of antitumor effects. The maximum tolerated dose

SUPPLEMENT ABSTRACTS

325

(MTD) was determined during the dose escalation part as Lonca 60 µg/

kg IV every 3 weeks (Q3W) for 2 cycles and oral ibrutinib 560 mg/day

po for up to 1 year. After disease assessment at Week 14, patients with

partial response or stable disease may receive 2 additional cycles of

Lonca every 4 weeks at Cycles 5 and 6.

Results: At data cut‐off (January 4, 2021), 30 patients with DLBCL (24

with non‐germinal center B‐cell [non‐GCB] DLBCL and 6 with GCB

DLBCL) and 7 patients with MCL had received the MTD. Median pa-

tient age was 72 years (range 40–91) and 28 (75.7%) had Stage 4

disease. Patients received a median of 2 (range 1–6) prior therapies.

Eight (21.6%) patients were primary refractory and 18 (48.6%) were

refractory to their last‐line of therapy; 24 (64.9%) and 17 (45.9%) had

relapsed with ﬁrst‐line and last‐line therapy, respectively.

Patients received a median of 2 Lonca cycles (range 1–4) and 4

(range 1–14) ibrutinib cycles. Median treatment duration was 105

days (range 18–379).

Treatment‐emergent adverse events (TEAEs) were reported in

37/37 (100%) patients; most common (≥20%) were thrombocytopenia

(11 [29.7%]), anemia (9 [24.3%]), fatigue, diarrhea, and rash (all 8

[21.6%]). Grade ≥3 TEAEs were reported in 24/37 (64.9%) patients;

most common (≥5%) were anemia (4 [10.8%]), neutropenia (4 [10.8%]),

thrombocytopenia (2 [5.4%]), and fatigue (2 [5.4%]). TEAEs leading to

treatment discontinuation occurred in 3 (8.1%) patients.

Overall response rate (ORR; in 36 evaluable patients) was 63.9%

(36.1% and 27.8% for complete and partial response, respectively).

ORR for patients with non‐GCB DLBCL, GCB DLBCL, all DLBCL, and

MCL was 66.7%, 20.0%, 58.6%, and 85.7%, respectively (Figure 1).

Conclusions: Results indicate that Lonca 60 µg/kg plus ibrutinib 560

mg has encouraging antitumor activity, with manageable toxicity in

R/R DLBCL or R/R MCL.

The research was funded by: ADC Therapeutics SA

Keywords: CombinationTherapies

Conﬂicts of interests pertinent to the abstract

J. Depaus

Consultant or advisory role: Takeda, Novartis, Janssen

N. Wagner‐Johnston

Consultant or advisory role: ADC Therapeutics, Regeneron, CALIB‐R,

Verastem, Karyopharm, Sanoﬁ, SeaGen, Epizyme, Grunenthal

P. L. Zinzani

Consultant or advisory role: Verastem, MSD, Eusapharma, Sanoﬁ.

ADC Therapeutics (advisory board agreement), Celltrion, Gilead,

Janssen‐Cilag, BMS, Servier, Sandoz, TG Therap., Takeda, Roche,

Kyowa Kirin

T. J. Phillips

Consultant or advisory role: Celgene/BMS, Kite/Gilead, Seattle Ge-

netics, Abbvie/Pharmacyclics, Incyte, Genentech

E. Bachy

Employment or leadership position: Université Claude Bernard Lyon

1, Lyon, France

Consultant or advisory role: Roche, Gilead

Honoraria: Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanoﬁ

L. J. Bryan

Employment or leadership position: Augusta University, Augusta, GA

M. Janakiram

Research funding: ADC Therapeutics, FATE Therapeutics, Takeda

Pharmaceuticals

S. de Guibert

Employment or leadership position: CHU Pontchaillou, Rennes,

France

Honoraria: Janssen, Abbvie, Gilead

V. Dai

Employment or leadership position: ADC Therapeutics; SUNY

Research Foundation

Stock ownership: ADC Therapeutics

K. Havenith

Employment or leadership position: ADC Therapeutics

Stock ownership: ADC Therapeutics

J. Boni

Employment or leadership position: ADC Therapeutics

Stock ownership: ADC Therapeutics

X. He

Employment or leadership position: ADC Therapeutics

Stock ownership: ADC Therapeutics

A. Ervin‐Haynes

Employment or leadership position: ADC Therapeutics

Stock ownership: ADC Therapeutics

C. Carlo‐Stella

Consultant or advisory role: Sanoﬁ, ADC Therapeutics, Roche, Kar-

yopharm Therapeutics, Celgene/Bristol‐Myers Squibb, Incyte

Honoraria: Bristol‐Myers Squibb, Janssen Oncology, AstraZeneca

FIGURE 1 ORR by histology

326

SUPPLEMENT ABSTRACTS

Research funding: ADC Therapeutics, Sanoﬁ, Roche

Educational grants: Roche, Janssen, Takeda, ADC Therapeutics

239 | FINAL ANALYSIS OF A NORDIC LYMPHOMA GROUP

PHASE IB/IIA TRIAL OF PIXANTRONE, ETOPOSIDE,

BENDAMUSTINE AND, IN CD20‐POSITIVE TUMORS, RITUXIMAB

IN RELAPSED AGGRESSIVE B‐ OR T‐CELL LYMPHOMAS

F. d'Amore

, S. Leppä

, T. Relander

, T. S. Larsen

, P. Brown

, J.

Jørgensen

, S. Mannisto

, P. Lugtenburg

, S.‐K. Leivonen

, H. Holte

U. M. Fagerli

, G. F. Lauritzsen

, P. Meyer

, G. Minotti

, P. Menna

K. Liestøl

, H. Toldbod

Aarhus University Hospital, Hematology, Aarhus N, Denmark,

Helsinki

University Hospital, Oncology, Helsinki, Finland,

Skane University

Hospital, Oncology, Lund, Sweden,

Odense University Hospital,

Hematology, Odense, Denmark,

Copenhagen University Hospital,

Hematology, Copenhagen, Denmark,

University Medical Center, Erasmus

MC Cancer Institute, Rotterdam, Netherlands,

Oslo University Hospital,

Oncology, Oslo, Norway,

St Olavs Hospital, Oncology, Trondheim,

Norway,

Stavanger University Hospital, Oncology, Stavanger, Norway,

University Hospital Campus Bio‐Medico, Clinical Pharmaclogy Labora-

tory, Rome, Italy,

University of Oslo, Informatics, Oslo, Norway

Introduction: Multiply relapsed aggressive lymphomas still represent

an unmet clinical need, particularly, if they occur in frail patients (pts).

We developed an out‐patient based salvage regimen consisting of

pixantrone, etoposide, bendamustine and, in CD20+ lymphomas,

rituximab (P[R]EBEN). Here we present the ﬁnal analysis of a phase

1b/2a trial testing this regimen in relapsed aggressive B‐ or T‐cell

lymphomas. Treatment refractory pts, i.e. duration of response

(DoR) since last treatment <6 months (mo), were excluded.

Methods and Results: Phase 1b: Five pts were included (median age:

60 yrs; range 39‐68 yrs). Four had diffuse large cell B‐cell (DLBCL) and

1 peripheral T‐cell lymphoma (PTCL). All had progressed after autol-

ogous transplant. The pharmacokinetics for pixantrone given in com-

bination (Fig.1a) resembled those of pixantrone monotherapy. Six

serious adverse events (SAEs) were reported among 4 pts: grade 1

(transitory asymptomatic troponin T elevation), grade 2 (non‐neu-

tropenic airways infection), grade 3 (non‐neutropenic fever, neu-

tropenic fever + anemia, pneumonia), grade 4 (septicemia). Two dose‐

limiting toxicities (DLTs; neutropenic infection and neutropenia <0.5 �

/l of >5 days duration) occurred within cycle 2 at baseline level,

meeting the criteria for maximum tolerated dose (MTD; primary

endpoint, phase1), and deﬁning the phase 2 dose level (P 50 mg/m

i.v.

day 1+8, R 375 mg/m

i.v. day 1, E 100 mg/m

i.v. day 1, Ben 90 mg/m

v. day 1).

Phase 2: Sixty pts (M/F ratio:1.3; age range:39‐84 yrs, median:71

yrs; 37 DLBCL and 23 PTCL) were enrolled and 58 were evaluable.

Median follow‐up was 33 mo (range 8‐53 mo). Grade 3‐4 hematologic

AEs included neutropenia 33%, thrombocytopenia 16%, and anemia

13%. Grade 3‐4 non‐hematological AEs included infections 33%, car-

diac 13% and other causes 27%. There were 31 deaths due to: lym-

phoma (22;71%), sepsis (2; 6%) and other causes (7; 23%: 1 lung

carcinoma, 1 acute leukemia, 1 myelodysplasia, 1 lung embolism, 1

allotransplant related and 2 unknown). Of 58 evaluable pts, 38 (66%)

had a complete (CR) and 1 (2%) a partial response, with an overall

response rate (primary endpoint, phase 2) of 68% (B: 51%; T: 70%) .

The median DoR (co‐primary endpoint, phase 2) of the 34 pts in CR at

end of treatment was 13 mo (range 0.5‐53+ mo; B: 13 mo; T: 12,5 mo).

Three pts were bridged to allogeneic transplant. The 3‐yr overall and

progression‐free survival (PFS) rates were 39% and 28%, respectively.

Pts with early metabolic response had a signiﬁcantly better PFS than

those with active disease (Fig.1b). A correlative analysis on pre‐

therapeutic biopsies is ongoing to identify gene expression signa-

tures in DLBCL and PTCL related to treatment response.

Conclusion: The P[R]EBEN regimen is a feasible out‐patient based

treatment, applicable in frail, heavily pre‐treated aggressive lym-

phoma pts and shows encouraging CR rates and DoR, particularly in

early responders.

The research was funded by: CTI Life Sciences Limited and Servier

Affaires Médicales

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Aggressive T‐

cell non‐Hodgkin lymphoma, Combination Therapies

No conﬂicts of interest pertinent to the abstract.

SUPPLEMENT ABSTRACTS

327

240 | MOSUNETUZUMAB MONOTHERAPY IN ELDERLY/UNFIT

PTS WITH FIRST‐LINE DIFFUSE LARGE B‐CELL LYMPHOMA

(DLBCL): SAFETY AND EFFICACY REMAIN PROMISING WITH

DURABLE COMPLETE RESPONSES

A. J. Olszewski

, A. Avigdor

, S. Babu

, I. Levi

, H. Eradat

, U. Abadi

H. Holmes

, M. McKinney

, D. Woszczyk

, K. Giannopoulos

, W.

Jurczak

, R. McCord

, Y. Xie

, K. Sarouei

, N. Qayum

, C.

O'Hear

, G. Sellam

, N. Horowitz

Alpert Medical School, Brown University, Department of Medicine,

Providence, Rhode Island, USA,

Sheba Medical Center, Division of

Hematology and Bone‐Marrow Transplantation, Ramat Gan, Israel,

Fort

Wayne Medical Oncology and Hematology, Division of Clinical Research,

Fort Wayne, Indiana, USA,

Soroka University Medical Centre, Depart-

ment of Hematology, Be’er‐Sheva, Israel,

University of California,

Department of Medicine, Los Angeles, California, USA,

Meir Medical

Center, Department of Hematology, Kfar Saba, Israel,

Texas Oncology,

Department of Oncology, Dallas, Texas, USA,

Duke Cancer Institute,

Division of Hematologic Malignancies and Cellular Therapy, Durham,

North Carolina, USA,

University of Opole, Provincial Hospital, Hematol-

ogy Department, Opole, Poland,

Medical University of Lublin, Depart-

ment of Experimental Hematooncology, Lublin, Poland,

Maria

Sklodowska‐Curie National Research Institute of Oncology, Department of

Hematology, Kraków, Poland,

Genentech, Inc., Oncology Biomarker

Development, South San Francisco, USA,

F. Hoffmann‐La Roche Ltd,

Department of Biometrics, Mississauga, Canada,

Genentech, Inc.,

Product Development Safety, South San Francisco, California, USA,

Roche Products Ltd, Product Development Oncology, Welwyn Garden

City, UK,

Genentech, Inc., Product Development Hematology, South San

Francisco, USA,

F. Hoffmann‐La Roche Ltd, Product Development

Oncology, Basel, Switzerland,

Ramban Healthcare Campus, Hematology

Division, Hifa, Israel

Introduction: Elderly/unﬁt pts with DLBCL, ineligible for standard

ﬁrst‐line (1L) chemoimmunotherapy (CIT) due to frailty and comor-

bidities, often receive no treatment, lower‐dose R‐CHOP, or thera-

pies such as R‐CVP or R‐bendamustine: outcomes are often poor.

Mosunetuzumab (Mosun), a full‐length, humanized, IgG1 CD20xCD3

bispeciﬁc antibody, has shown promise in relapsed/refractory DLBCL

(ongoing Ph 1 study NCT02500407). Early data from the Ph 1/2,

multicenter GO40554 study (NCT03677154) show notable efﬁcacy

and tolerability with Mosun monotherapy in elderly/unﬁt pts with 1L

DLBCL. We report updated GO40554 data.

Methods: Two safety‐evaluation cohorts were assessed (Mosun

13.5mg and 30mg) followed by an expansion phase (30mg). Pts aged

≥80 yr, or 60–79 yr with ≥1 activity of daily living (ADL) impaired or

instrumental ADL, or reduced cardiac, renal or liver function pre-

cluding full‐dose CIT, received optional prednisone (± vincristine)

pre‐treatment, then IV Mosun on Days (D) 1 (1mg), 8 (2mg) and 15

(13.5 or 30mg) of Cycle (C) 1 and 13.5 or 30mg Mosun on D1 of each

subsequent 21‐day cycle. Pts with a complete response (CR) stop at 8

cycles; pts with a partial response (PR) or stable disease can continue

to 17 cycles.

Results: By Jan 15 2021, 40 pts received Mosun (13.5mg, n = 8; 30mg ,

n = 7; 30mg expansion, n = 25). Median age was 84 yr (67–100); 27

(67.5%) pts were female, 27 (67.5%) had ECOG‐PS 0–1, 20 (50%) had

Ann Arbor Stage III–IV and 32 (80%) had an IPI score ≥2. Pts received a

median of 6 (1–13) cycles; 2 pts in PR continued after C8. 35/40

(87.5%) pts had ≥1 adverse event (AE), 27 (67.5%) had ≥1 Mosun‐

related AE; 15 (37.5%) had a grade (Gr) 3–4 AE (8 Mosun‐related).

Common (>10%) treatment‐emergent AEs were cytokine release

syndrome (CRS; n = 9, 22.5%), abdominal pain (n = 7, 17.5%), rash (n =

5, 12.5%) and neutropenia (n = 5, 12.5%); 1 pt had febrile neutropenia.

6 (15%) pts had Gr 1 CRS by ASTCT. 3 (7.5%) pts had Gr 2 CRS, all

managed with supportive care, ﬂuids for hypotension, steroids and

low‐ﬂow O

, as needed (no tocilizumab, vasopressors, high‐ﬂow O

intensive care required). One Gr 1 CRS pt had Mosun‐related Gr 2

neurotoxicity on C1D2 (inability to answer questions, drowsiness and

weakness), resolving after 2 days. 1 pt had a Gr 2 non‐serious head-

ache. No pts had fatal or Gr ≥3 neurologic AEs. From C1–8, 14 (35%)

pts discontinued Mosun due to progressive disease (PD); none dis-

continued due to AEs. Overall response rate in efﬁcacy‐evaluable pts

(n = 31) was 67.7%; CR rate was 41.9%. Responses post C8 (n [%]) with

Mosun 13.5mg (n = 8) were: 3 (37.5) CR; 3 (37.5) PR; 2 (25) PD; and

post C4 or C8 with Mosun 30mg (n = 23) were: 10 (43.5) CR; 5 (21.7)

PR; 3 (13) PD. Of 13 pts with CR (11 ongoing), 4 durable responses

were seen ≥12 months from therapy initiation (Figure).

Conclusions: Mosun shows promising efﬁcacy with durable re-

sponses and tolerable safety in elderly/unﬁt pts with 1L DLBCL and

should be evaluated as a CIT‐free option.

EA – previously submitted to EHA 2021.

The research was funded by: F. Hoffmann‐La Roche Ltd/Genentech,

Inc. Third‐party medical writing assistance, under the direction of the

authors, was provided by Katie Buxton and Khalida Rizi of Ashﬁeld

MedComms, an Ashﬁeld Health company, and funded by F.

Hoffmann‐La Roche Ltd/Genentech, Inc.

Keywords: Aggressive B‐cell non‐Hodgkin lymphoma, Immunotherapy

Conﬂicts of interests pertinent to the abstract

A. J. Olszewski

Research funding: F. Hoffmann‐La Roche Ltd/Genentech, Inc., TG

Therapeutics, Adaptive Biotechnologies, Celldex Therapeutics, Pre-

cisionBio, Genmab

A. Avigdor

Consultant or advisory role: Takeda, F. Hoffmann‐La Roche Ltd,

Gilead, Pﬁzer

Educational grants: Takeda

Other remuneration: Speakers' bureau: Takeda

S. Babu

Employment or leadership position: Fort Wayne Medical Oncology &

Hematology

328

SUPPLEMENT ABSTRACTS

Consultant or advisory role: Bristol‐Myers Squibb, Alexion Pharma-

ceuticals, AstraZeneca, argenx, Boehringer Ingelheim, Bayer, Kite

Pharma, Janssen Oncology, Amgen

Stock ownership: Lutheran hospital, Fort Wayne Medical Oncology &

Hematology

Honoraria: Bristol‐Myers Squibb, Alexion Pharmaceuticals, Lilly,

Bayer, AstraZeneca

Research funding: Bristol‐Myers Squibb, Novartis, Genentech, Inc./F.

Hoffmann‐La Roche Ltd, AstraZeneca/MedImmune, Janssen

Oncology, Amgen, TG Therapeutics, AbbVie, Lilly, Alexion Pharma-

ceuticals, Merck, Syndax, Nektar, Sanoﬁ, argenx

Educational grants: Bristol‐Myers Squibb, Alexion Pharmaceuticals,

Lilly, Janssen Oncology, Genentech, Inc./F. Hoffmann‐La Roche Ltd

Other remuneration: Speakers' bureau: Alexion Pharmaceuticals

H. Eradat

Employment or leadership position: UCLA Medical Center, David

Geffen School of Medicine at UCLA

Consultant or advisory role: Genentech, Inc., F. Hoffmann‐La Roche

Ltd, AbbVie

Honoraria: Genentech, Inc., AbbVie

Research funding: Genentech, Inc., F. Hoffmann‐La Roche Ltd, Abb-

Vie, AstraZeneca, Atara, Kite, Juno, Acerta, BeiGene, Celgene

Other remuneration: Speakers bureau: Genentech, Inc., AbbVie

U. Abadi

Consultant or advisory role: F. Hoffmann‐La Roche Ltd

Educational grants: F. Hoffmann‐La Roche Ltd

H. Holmes

Consultant or advisory role: Kite, Novartis, TG Therapeutics, ADC

Therapeutics, Rigel, Dova, Janssen, Bristol‐Myers Squibb

Other remuneration: Speakers' bureau: Kite, Karyopharm, Dova,

Rigel

M. McKinney

Consultant or advisory role: Kite/Gilead, Seattle Genetics, Molecular

Templates, BTG, Pharmacyclics, Verastem, Genentech, Inc., Celgene

Honoraria: Kite/Gilead

Research funding: UNUM, Molecular Templates, Incyte, BeiGene,

Denovo Biopharma, Pharmacyclics, Nordic Nanovector, Bristol‐

Myers Squibb, Genentech, Inc., Celgene

Other remuneration: Speakers' bureau: Kite/Gilead

D. Woszczyk

Honoraria: F. Hoffmann‐La Roche Ltd

Research funding: Millenium, Takeda, Janssen‐Cilag, Novartis, Acerta

Pharma

K. Giannopoulos

Honoraria: F. Hoffmann‐La Roche Ltd

Educational grants: F. Hoffmann‐La Roche Ltd

W. Jurczak

Research funding: F. Hoffmann‐La Roche Ltd

R. McCord

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann‐La Roche Ltd

Y. Xie

Employment or leadership position: F. Hoffmann‐La Roche Ltd

K. Sarouei

Employment or leadership position: Genentech, Inc.

Stock ownership: F. Hoffmann‐La Roche Ltd

N. Qayum

Employment or leadership position: F. Hoffmann‐La Roche Ltd

Stock ownership: F. Hoffmann‐La Roche Ltd

FIGURE:

Duration of response and time on study by Mosun dosing cohorts

SUPPLEMENT ABSTRACTS

329